{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T15:23:32Z","timestamp":1794583412447,"version":"4.9.1"},"reference-count":129,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG074569"],"award-info":[{"award-number":["RF1AG074569"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG047266"],"award-info":[{"award-number":["P30 AG047266"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Extracellular deposits of amyloid-\u03b2 (A\u03b2) in the form of plaques are one of the main pathological hallmarks of Alzheimer\u2019s disease (AD). Over the years, many different A\u03b2 plaque morphologies such as neuritic plaques, dense cored plaques, cotton wool plaques, coarse-grain plaques, and diffuse plaques have been described in AD postmortem brain tissues, but correlation of a given plaque type with AD progression or AD symptoms is not clear. Furthermore, the exact trigger causing the development of one A\u03b2 plaque morphological subtype over the other is still unknown. Here, we review the current knowledge about neuritic plaques, a subset of A\u03b2 plaques surrounded by swollen or dystrophic neurites, which represent the most detrimental and consequential A\u03b2 plaque morphology. Neuritic plaques have been associated with local immune activation, neuronal network dysfunction, and cognitive decline. Given that neuritic plaques are at the interface of A\u03b2 deposition, tau aggregation, and local immune activation, we argue that understanding the exact mechanism of neuritic plaque formation is crucial to develop targeted therapies for AD.<\/jats:p>","DOI":"10.1007\/s12035-023-03736-7","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T15:01:22Z","timestamp":1699455682000},"page":"2808-2821","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Neuritic Plaques \u2014 Gateways to Understanding Alzheimer\u2019s Disease"],"prefix":"10.1007","volume":"61","author":[{"given":"Wangchen","family":"Tsering","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-2149","authenticated-orcid":false,"given":"Stefan","family":"Prokop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"3736_CR1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s13311-021-01146-y","volume":"19","author":"JA Trejo-Lopez","year":"2022","unstructured":"Trejo-Lopez JA, Yachnis AT, Prokop S (2022) Neuropathology of Alzheimer\u2019s disease. Neurotherapeutics 19:173\u2013185. https:\/\/doi.org\/10.1007\/s13311-021-01146-y","journal-title":"Neurotherapeutics"},{"key":"3736_CR2","doi-asserted-by":"publisher","first-page":"a006296","DOI":"10.1101\/cshperspect.a006296","volume":"2","author":"RE Tanzi","year":"2012","unstructured":"Tanzi RE (2012) The genetics of Alzheimer disease. Cold Spring Harb Perspect Med 2:a006296. https:\/\/doi.org\/10.1101\/cshperspect.a006296","journal-title":"Cold Spring Harb Perspect Med"},{"key":"3736_CR3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1750-1326-6-27","volume":"6","author":"H Zheng","year":"2011","unstructured":"Zheng H, Koo EH (2011) Biology and pathophysiology of the amyloid precursor protein. Mol Neurodegener 6:27. https:\/\/doi.org\/10.1186\/1750-1326-6-27","journal-title":"Mol Neurodegener"},{"key":"3736_CR4","doi-asserted-by":"publisher","first-page":"a006304","DOI":"10.1101\/cshperspect.a006304","volume":"2","author":"B De Strooper","year":"2012","unstructured":"De Strooper B, Iwatsubo T, Wolfe MS (2012) Presenilins and \u03b3-secretase: structure, function, and role in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006304\u2013a006304. https:\/\/doi.org\/10.1101\/cshperspect.a006304","journal-title":"Cold Spring Harb Perspect Med"},{"key":"3736_CR5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1006\/nbdi.1996.0003","volume":"3","author":"CA Lemere","year":"1996","unstructured":"Lemere CA, Blusztajn JK, Yamaguchi H et al (1996) Sequence of deposition of heterogeneous amyloid \u03b2-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Dis 3:16\u201332. https:\/\/doi.org\/10.1006\/nbdi.1996.0003","journal-title":"Neurobiol Dis"},{"key":"3736_CR6","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/nature11283","volume":"488","author":"T Jonsson","year":"2012","unstructured":"Jonsson T, Atwal JK, Steinberg S et al (2012) A mutation in APP protects against Alzheimer\u2019s disease and age-related cognitive decline. Nature 488:96\u201399. https:\/\/doi.org\/10.1038\/nature11283","journal-title":"Nature"},{"key":"3736_CR7","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol Med 8:595\u2013608. https:\/\/doi.org\/10.15252\/emmm.201606210","journal-title":"EMBO Mol Med"},{"key":"3736_CR8","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer\u2019s disease: progress and problems on the road to therapeutics. Science 297:353\u2013356. https:\/\/doi.org\/10.1126\/science.1072994","journal-title":"Science"},{"key":"3736_CR9","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/0165-6147(91)90609-v","volume":"12","author":"J Hardy","year":"1991","unstructured":"Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer\u2019s disease. Trends Pharmacol Sci 12:383\u2013388. https:\/\/doi.org\/10.1016\/0165-6147(91)90609-v","journal-title":"Trends Pharmacol Sci"},{"key":"3736_CR10","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","volume":"164","author":"B De Strooper","year":"2016","unstructured":"De Strooper B, Karran E (2016) The cellular phase of Alzheimer\u2019s disease. Cell 164:603\u2013615. https:\/\/doi.org\/10.1016\/j.cell.2015.12.056","journal-title":"Cell"},{"key":"3736_CR11","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1093\/BRAIN\/AWY146","volume":"141","author":"JL Robinson","year":"2018","unstructured":"Robinson JL, Lee EB, Xie SX et al (2018) Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain 141:2181\u20132193. https:\/\/doi.org\/10.1093\/BRAIN\/AWY146","journal-title":"Brain"},{"key":"3736_CR12","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1385\/JMN:17:2:225","volume":"17","author":"PT Kotzbauer","year":"2001","unstructured":"Kotzbauer PT, Trojanowski JQ, Lee VMY (2001) Lewy body pathology in Alzheimer\u2019s disease. J Mol Neurosci 17:225\u2013232. https:\/\/doi.org\/10.1385\/JMN:17:2:225","journal-title":"J Mol Neurosci"},{"key":"3736_CR13","doi-asserted-by":"publisher","unstructured":"Twohig D, Nielsen HM (2019) \u03b1-synuclein in the pathophysiology of Alzheimer\u2019s disease. Mol Neurodegener 14. https:\/\/doi.org\/10.1186\/S13024-019-0320-X","DOI":"10.1186\/S13024-019-0320-X"},{"key":"3736_CR14","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/0197-4580(92)90027-u","volume":"13","author":"DW Dickson","year":"1992","unstructured":"Dickson DW, Crystal HA, Mattiace LA et al (1992) Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol Aging 13:179\u2013189. https:\/\/doi.org\/10.1016\/0197-4580(92)90027-u","journal-title":"Neurobiol Aging"},{"key":"3736_CR15","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s00401-014-1349-0","volume":"128","author":"JF Crary","year":"2014","unstructured":"Crary JF, Trojanowski JQ, Schneider JA et al (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755\u2013766. https:\/\/doi.org\/10.1007\/s00401-014-1349-0","journal-title":"Acta Neuropathol"},{"key":"3736_CR16","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1212\/wnl.58.12.1791","volume":"58","author":"DR Thal","year":"2002","unstructured":"Thal DR, R\u00fcb U, Orantes M, Braak H (2002) Phases of A\u03b2-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791\u20131800. https:\/\/doi.org\/10.1212\/wnl.58.12.1791","journal-title":"Neurology"},{"key":"3736_CR17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/bf00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239\u2013259. https:\/\/doi.org\/10.1007\/bf00308809","journal-title":"Acta Neuropathol"},{"key":"3736_CR18","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0B013E318232A379","volume":"70","author":"H Braak","year":"2011","unstructured":"Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 70:960\u2013969. https:\/\/doi.org\/10.1097\/NEN.0B013E318232A379","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR19","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nm0498-452","volume":"4","author":"R Crook","year":"1998","unstructured":"Crook R, Verkkoniemi A, Perez-Tur J et al (1998) A variant of Alzheimer\u2019s disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1. Nat Med 4:452\u2013455. https:\/\/doi.org\/10.1038\/nm0498-452","journal-title":"Nat Med"},{"key":"3736_CR20","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1007\/s00401-020-02198-8","volume":"140","author":"BDC Boon","year":"2020","unstructured":"Boon BDC, Bulk M, Jonker AJ et al (2020) The coarse-grained plaque: a divergent A\u03b2 plaque-type in early-onset Alzheimer\u2019s disease. Acta Neuropathol 140:811\u2013830. https:\/\/doi.org\/10.1007\/s00401-020-02198-8","journal-title":"Acta Neuropathol"},{"key":"3736_CR21","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s00401-022-02500-w","volume":"144","author":"S Ichimata","year":"2022","unstructured":"Ichimata S, Martinez-Valbuena I, Forrest SL, Kovacs GG (2022) Expanding the spectrum of amyloid-\u03b2 plaque pathology: the Down syndrome associated \u2018bird-nest plaque. Acta Neuropathol 144:1171\u20131174. https:\/\/doi.org\/10.1007\/s00401-022-02500-w","journal-title":"Acta Neuropathol"},{"key":"3736_CR22","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/s0306-4522(01)00169-5","volume":"105","author":"TC Dickson","year":"2001","unstructured":"Dickson TC, Vickers JC (2001) The morphological phenotype of \u03b2-amyloid plaques and associated neuritic changes in Alzheimer\u2019s disease. Neuroscience 105:99\u2013107. https:\/\/doi.org\/10.1016\/s0306-4522(01)00169-5","journal-title":"Neuroscience"},{"key":"3736_CR23","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1097\/00005072-199807000-00004","volume":"57","author":"HM Wisniewski","year":"1998","unstructured":"Wisniewski HM, Sadowski M, Jakubowska-Sadowswka K et al (1998) Diffuse, lake-like amyloid-\u03b2 deposits in the parvopyramidal layer of the presubiculum in Alzheimer disease. J Neuropathol Exp Neurol 57:674\u2013683. https:\/\/doi.org\/10.1097\/00005072-199807000-00004","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR24","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1097\/00005072-198905000-00093","volume":"48","author":"C Joachim","year":"1989","unstructured":"Joachim C, Morris J, Platt D, Selkoe D (1989) Diffuse senile plaques. J Neuropathol Exp Neurol 48:330. https:\/\/doi.org\/10.1097\/00005072-198905000-00093","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR25","volume-title":"Reexamination of the pathogenesis of the senile plaque","author":"HMTR Wisniewski","year":"1973","unstructured":"Wisniewski HMTR (1973) Reexamination of the pathogenesis of the senile plaque. Pog Neuropathol"},{"key":"3736_CR26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.nbd.2003.09.007","volume":"15","author":"A Boutajangout","year":"2004","unstructured":"Boutajangout A, Authelet M, Blanchard V et al (2004) Characterisation of cytoskeletal abnormalities in mice transgenic for wild-type human tau and familial Alzheimer\u2019s disease mutants of APP and presenilin-1. Neurobiol Dis 15:47\u201360. https:\/\/doi.org\/10.1016\/j.nbd.2003.09.007","journal-title":"Neurobiol Dis"},{"key":"3736_CR27","doi-asserted-by":"publisher","first-page":"106150","DOI":"10.1016\/j.nbd.2023.106150","volume":"182","author":"R Mabrouk","year":"2023","unstructured":"Mabrouk R, Miettinen PO, Tanila H (2023) Most dystrophic neurites in the common 5xFAD Alzheimer mouse model originate from axon terminals. Neurobiol Dis 182:106150. https:\/\/doi.org\/10.1016\/j.nbd.2023.106150","journal-title":"Neurobiol Dis"},{"key":"3736_CR28","doi-asserted-by":"publisher","first-page":"8552","DOI":"10.1523\/JNEUROSCI.19-19-08552.1999","volume":"19","author":"AL Phinney","year":"1999","unstructured":"Phinney AL, Deller T, Stalder M et al (1999) Cerebral amyloid induces aberrant axonal sprouting and ectopic terminal formation in amyloid precursor protein transgenic mice. J Neurosci 19:8552\u20138559. https:\/\/doi.org\/10.1523\/JNEUROSCI.19-19-08552.1999","journal-title":"J Neurosci"},{"key":"3736_CR29","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/0006-8993(93)91063-x","volume":"625","author":"JH Su","year":"1993","unstructured":"Su JH, Cummings BJ, Cotman CW (1993) Identification and distribution of axonal dystrophic neurites in Alzheimer\u2019s disease. Brain Res 625:228\u2013237. https:\/\/doi.org\/10.1016\/0006-8993(93)91063-x","journal-title":"Brain Res"},{"key":"3736_CR30","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1097\/00005072-199311000-00009","volume":"52","author":"E Masliah","year":"1993","unstructured":"Masliah E, Mallory M, Deerinck T et al (1993) Re-evaluation of the structural organization of neuritic plaques in Alzheimer\u02bcs disease. J Neuropathol Exp Neurol 52:619\u2013632. https:\/\/doi.org\/10.1097\/00005072-199311000-00009","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR31","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1093\/jnen\/59.8.733","volume":"59","author":"DR Thal","year":"2000","unstructured":"Thal DR, R\u00fcb U, Schultz C et al (2000) Sequence of A\u03b2-protein deposition in the human medial temporal lobe. J Neuropathol; Exp Neurol 59:733\u2013748. https:\/\/doi.org\/10.1093\/jnen\/59.8.733","journal-title":"J Neuropathol; Exp Neurol"},{"key":"3736_CR32","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1111\/j.1749-6632.1991.tb00203.x","volume":"640","author":"O Bugiani","year":"1991","unstructured":"Bugiani O, Tagliavini F, Giaccone G (1991) Preamyloid deposits, amyloid deposits, and senile plaques in Alzheimer\u2019s disease, down syndrome, and aging. Ann N Y Acad Sci 640:122\u2013128. https:\/\/doi.org\/10.1111\/j.1749-6632.1991.tb00203.x","journal-title":"Ann N Y Acad Sci"},{"key":"3736_CR33","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40478-017-0415-y","volume":"5","author":"L Blazquez-Llorca","year":"2017","unstructured":"Blazquez-Llorca L, Valero-Freitag S, Rodrigues EF et al (2017) High plasticity of axonal pathology in Alzheimer\u2019s disease mouse models. Acta Neuropathol Commun 5:14. https:\/\/doi.org\/10.1186\/s40478-017-0415-y","journal-title":"Acta Neuropathol Commun"},{"key":"3736_CR34","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1172\/JCI23269","volume":"115","author":"RP Brendza","year":"2005","unstructured":"Brendza RP, Bacskai BJ, Cirrito JR et al (2005) Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice. J Clin Invest 115:428\u2013433. https:\/\/doi.org\/10.1172\/JCI23269","journal-title":"J Clin Invest"},{"key":"3736_CR35","doi-asserted-by":"publisher","unstructured":"Xu G, Fromholt S, Borchelt DR (2022) Modeling the competition between misfolded A\u03b2 conformers that produce distinct types of amyloid pathology in Alzheimer\u2019s disease. Biomolecules 12. https:\/\/doi.org\/10.3390\/biom12070886","DOI":"10.3390\/biom12070886"},{"key":"3736_CR36","doi-asserted-by":"publisher","unstructured":"Xu G, Fromholt SE, Chakrabarty P et al (2020) Diversity in A\u03b2 deposit morphology and secondary proteome insolubility across models of Alzheimer-type amyloidosis. Acta Neuropathol Commun 8. https:\/\/doi.org\/10.1186\/S40478-020-00911-Y","DOI":"10.1186\/S40478-020-00911-Y"},{"key":"3736_CR37","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1126\/SCIENCE.1131864","volume":"313","author":"M Meyer-Luehmann","year":"2006","unstructured":"Meyer-Luehmann M, Coomaraswamy J, Bolmont T et al (2006) Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 313:1781\u20131784. https:\/\/doi.org\/10.1126\/SCIENCE.1131864","journal-title":"Science"},{"key":"3736_CR38","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13024-022-00523-1","volume":"17","author":"TE Golde","year":"2022","unstructured":"Golde TE (2022) Alzheimer\u2019s disease - the journey of a healthy brain into organ failure. Mol Neurodegener 17:18. https:\/\/doi.org\/10.1186\/s13024-022-00523-1","journal-title":"Mol Neurodegener"},{"key":"3736_CR39","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s00429-007-0153-1","volume":"212","author":"JC Fiala","year":"2007","unstructured":"Fiala JC, Feinberg M, Peters A, Barbas H (2007) Mitochondrial degeneration in dystrophic neurites of senile plaques may lead to extracellular deposition of fine filaments. Brain Struct Funct 212:195\u2013207. https:\/\/doi.org\/10.1007\/s00429-007-0153-1","journal-title":"Brain Struct Funct"},{"key":"3736_CR40","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s40478-019-0861-9","volume":"7","author":"CM Kelley","year":"2019","unstructured":"Kelley CM, Perez SE, Mufson EJ (2019) Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study. Acta Neuropathol Commun 7:207. https:\/\/doi.org\/10.1186\/s40478-019-0861-9","journal-title":"Acta Neuropathol Commun"},{"key":"3736_CR41","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.expneurol.2016.02.007","volume":"287","author":"ST Carmichael","year":"2017","unstructured":"Carmichael ST, Kathirvelu B, Schweppe CA, Nie EH (2017) Molecular, cellular and functional events in axonal sprouting after stroke. Exp Neurol 287:384\u2013394. https:\/\/doi.org\/10.1016\/j.expneurol.2016.02.007","journal-title":"Exp Neurol"},{"key":"3736_CR42","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.eplepsyres.2006.03.006","volume":"70","author":"AR Judkins","year":"2006","unstructured":"Judkins AR, Porter BE, Cook N et al (2006) Dystrophic neuritic processes in epileptic cortex. Epilepsy Res 70:49\u201358. https:\/\/doi.org\/10.1016\/j.eplepsyres.2006.03.006","journal-title":"Epilepsy Res"},{"key":"3736_CR43","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1093\/brain\/awn312","volume":"132","author":"R Adalbert","year":"2008","unstructured":"Adalbert R, Nogradi A, Babetto E et al (2008) Severely dystrophic axons at amyloid plaques remain continuous and connected to viable cell bodies. Brain 132:402\u2013416. https:\/\/doi.org\/10.1093\/brain\/awn312","journal-title":"Brain"},{"key":"3736_CR44","doi-asserted-by":"publisher","first-page":"5274","DOI":"10.1073\/pnas.96.9.5274","volume":"96","author":"RB Knowles","year":"1999","unstructured":"Knowles RB, Wyart C, Buldyrev SV et al (1999) Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer\u2019s disease. Proc Natl Acad Sci U S A 96:5274\u20135279. https:\/\/doi.org\/10.1073\/pnas.96.9.5274","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3736_CR45","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1093\/jnen\/60.8.753","volume":"60","author":"R Le","year":"2001","unstructured":"Le R, Cruz L, Urbanc B et al (2001) Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease: implications for neural system disruption. J Neuropathol Exp Neurol 60:753\u2013758. https:\/\/doi.org\/10.1093\/jnen\/60.8.753","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR46","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41586-022-05491-6","volume":"612","author":"P Yuan","year":"2022","unstructured":"Yuan P, Zhang M, Tong L et al (2022) PLD3 affects axonal spheroids and network defects in Alzheimer\u2019s disease. Nature 612:328\u2013337. https:\/\/doi.org\/10.1038\/s41586-022-05491-6","journal-title":"Nature"},{"key":"3736_CR47","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1001\/archneur.55.9.1185","volume":"55","author":"V Haroutunian","year":"1998","unstructured":"Haroutunian V (1998) Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease. Arch Neurol 55:1185\u20131191. https:\/\/doi.org\/10.1001\/archneur.55.9.1185","journal-title":"Arch Neurol"},{"key":"3736_CR48","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.3233\/JAD-160365","volume":"53","author":"M Malek-Ahmadi","year":"2016","unstructured":"Malek-Ahmadi M, Perez SE, Chen K, Mufson EJ (2016) Neuritic and diffuse plaque associations with memory in non-cognitively impaired elderly. J Alzheimers Dis 53:1641\u20131652. https:\/\/doi.org\/10.3233\/JAD-160365","journal-title":"J Alzheimers Dis"},{"key":"3736_CR49","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","volume":"71","author":"PT Nelson","year":"2012","unstructured":"Nelson PT, Alafuzoff I, Bigio EH et al (2012) Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 71:362\u2013381. https:\/\/doi.org\/10.1097\/NEN.0b013e31825018f7","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR50","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/j.1750-3639.2008.00244.x","volume":"20","author":"PT Nelson","year":"2010","unstructured":"Nelson PT, Abner EL, Schmitt FA et al (2010) Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol 20:66\u201379. https:\/\/doi.org\/10.1111\/j.1750-3639.2008.00244.x","journal-title":"Brain Pathol"},{"key":"3736_CR51","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s00401-013-1182-x","volume":"126","author":"S Prokop","year":"2013","unstructured":"Prokop S, Miller KR, Heppner FL (2013) Microglia actions in Alzheimer\u2019s disease. Acta Neuropathol 126:461\u2013477. https:\/\/doi.org\/10.1007\/s00401-013-1182-x","journal-title":"Acta Neuropathol"},{"key":"3736_CR52","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1038\/s41591-021-01456-w","volume":"27","author":"TA Pascoal","year":"2021","unstructured":"Pascoal TA, Benedet AL, Ashton NJ et al (2021) Microglial activation and tau propagate jointly across Braak stages. Nat Med 27:1592\u20131599. https:\/\/doi.org\/10.1038\/s41591-021-01456-w","journal-title":"Nat Med"},{"key":"3736_CR53","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/0304-3940(87)90696-3","volume":"79","author":"PL McGeer","year":"1987","unstructured":"McGeer PL, Itagaki S, Tago H, McGeer EG (1987) Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett 79:195\u2013200. https:\/\/doi.org\/10.1016\/0304-3940(87)90696-3","journal-title":"Neurosci Lett"},{"key":"3736_CR54","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/bf00687883","volume":"77","author":"S Haga","year":"1989","unstructured":"Haga S, Akai K, Ishii T (1989) Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. Acta Neuropathol 77:569\u2013575. https:\/\/doi.org\/10.1007\/bf00687883","journal-title":"Acta Neuropathol"},{"key":"3736_CR55","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1007\/bf00305864","volume":"81","author":"T Ohgami","year":"1991","unstructured":"Ohgami T, Kitamoto T, Shin RW et al (1991) Increased senile plaques without microglia in Alzheimer\u2019s disease. Acta Neuropathol 81:242\u2013247. https:\/\/doi.org\/10.1007\/bf00305864","journal-title":"Acta Neuropathol"},{"key":"3736_CR56","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/0197-4580(95)00092-s","volume":"16","author":"IRA Mackenzie","year":"1995","unstructured":"Mackenzie IRA, Hao C, Munoz DG (1995) Role of microglia in senile plaque formation. Neurobiol Aging 16:797\u2013804. https:\/\/doi.org\/10.1016\/0197-4580(95)00092-s","journal-title":"Neurobiol Aging"},{"key":"3736_CR57","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13024-018-0244-x","volume":"13","author":"J Sosna","year":"2018","unstructured":"Sosna J, Philipp S, Albay R 3rd et al (2018) Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer\u2019s disease. Mol Neurodegener 13:11. https:\/\/doi.org\/10.1186\/s13024-018-0244-x","journal-title":"Mol Neurodegener"},{"key":"3736_CR58","doi-asserted-by":"publisher","first-page":"110961","DOI":"10.1016\/j.celrep.2022.110961","volume":"39","author":"A Sepideh Kiani Shabestari","year":"2022","unstructured":"Sepideh Kiani Shabestari A, Morabito S, Pascal Danhash E et al (2022) Absence of microglia promotes diverse pathologies and early lethality in Alzheimer\u2019s disease mice. CellReports 39:110961. https:\/\/doi.org\/10.1016\/j.celrep.2022.110961","journal-title":"CellReports"},{"key":"3736_CR59","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s00401-019-02048-2","volume":"138","author":"S Prokop","year":"2019","unstructured":"Prokop S, Miller KR, Labra SR et al (2019) Impact of TREM2 risk variants on brain region-specific immune activation and plaque microenvironment in Alzheimer\u2019s disease patient brain samples. Acta Neuropathol 138:613\u2013630. https:\/\/doi.org\/10.1007\/s00401-019-02048-2","journal-title":"Acta Neuropathol"},{"key":"3736_CR60","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1038\/s41593-019-0433-0","volume":"22","author":"CEG Leyns","year":"2019","unstructured":"Leyns CEG, Gratuze M, Narasimhan S et al (2019) TREM2 function impedes tau seeding in neuritic plaques. Nat Neurosci 22:1217\u20131222. https:\/\/doi.org\/10.1038\/s41593-019-0433-0","journal-title":"Nat Neurosci"},{"key":"3736_CR61","doi-asserted-by":"publisher","first-page":"e20220654","DOI":"10.1084\/jem.20220654","volume":"220","author":"N Jain","year":"2023","unstructured":"Jain N, Lewis CA, Ulrich JD, Holtzman DM (2023) Chronic TREM2 activation exacerbates A\u03b2-associated tau seeding and spreading. J Exp Med 220:e20220654. https:\/\/doi.org\/10.1084\/jem.20220654","journal-title":"J Exp Med"},{"key":"3736_CR62","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.nbd.2014.07.011","volume":"71","author":"A Pensalfini","year":"2014","unstructured":"Pensalfini A, Albay R 3rd, Rasool S et al (2014) Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques. Neurobiol Dis 71:53\u201361. https:\/\/doi.org\/10.1016\/j.nbd.2014.07.011","journal-title":"Neurobiol Dis"},{"key":"3736_CR63","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1046\/j.1365-2559.2001.01082.x","volume":"38","author":"MR D\u2019Andrea","year":"2001","unstructured":"D\u2019Andrea MR, Nagele RG, Wang H-Y et al (2001) Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer\u2019s disease. Histopathology 38:120\u2013134. https:\/\/doi.org\/10.1046\/j.1365-2559.2001.01082.x","journal-title":"Histopathology"},{"key":"3736_CR64","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.neuron.2022.10.021","volume":"111","author":"J Hu","year":"2023","unstructured":"Hu J, Chen Q, Zhu H et al (2023) Microglial Piezo1 senses A\u03b2 fibril stiffness to restrict Alzheimer\u2019s disease. Neuron 111:15-29.e8. https:\/\/doi.org\/10.1016\/j.neuron.2022.10.021","journal-title":"Neuron"},{"key":"3736_CR65","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S1474-4422(18)30490-3","volume":"18","author":"AM Arranz","year":"2019","unstructured":"Arranz AM, De Strooper B (2019) The role of astroglia in Alzheimer\u2019s disease: pathophysiology and clinical implications. Lancet Neurol 18:406\u2013414. https:\/\/doi.org\/10.1016\/S1474-4422(18)30490-3","journal-title":"Lancet Neurol"},{"key":"3736_CR66","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1002\/glia.440020605","volume":"2","author":"TG Beach","year":"1989","unstructured":"Beach TG, Walker R, McGeer EG (1989) Patterns of gliosis in Alzheimer\u2019s disease and aging cerebrum. Glia 2:420\u2013436. https:\/\/doi.org\/10.1002\/glia.440020605","journal-title":"Glia"},{"key":"3736_CR67","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1097\/NEN.0b013e3182933788","volume":"72","author":"A Serrano-Pozo","year":"2013","unstructured":"Serrano-Pozo A, Muzikansky A, G\u00f3mez-Isla T et al (2013) Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease. J Neuropathol Exp Neurol 72:462\u2013471. https:\/\/doi.org\/10.1097\/NEN.0b013e3182933788","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR68","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/glia.23270","volume":"66","author":"A Gomez-Arboledas","year":"2018","unstructured":"Gomez-Arboledas A, Davila JC, Sanchez-Mejias E et al (2018) Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer\u2019s disease. Glia 66:637\u2013653. https:\/\/doi.org\/10.1002\/glia.23270","journal-title":"Glia"},{"key":"3736_CR69","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/nm.4443","volume":"24","author":"Z He","year":"2018","unstructured":"He Z, Guo JL, McBride JD et al (2018) Amyloid-\u03b2 plaques enhance Alzheimer\u2019s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24:29\u201338. https:\/\/doi.org\/10.1038\/nm.4443","journal-title":"Nat Med"},{"key":"3736_CR70","doi-asserted-by":"publisher","first-page":"12082","DOI":"10.1038\/ncomms12082","volume":"7","author":"T Li","year":"2016","unstructured":"Li T, Braunstein KE, Zhang J et al (2016) The neuritic plaque facilitates pathological conversion of tau in an Alzheimer\u2019s disease mouse model. Nat Commun 7:12082. https:\/\/doi.org\/10.1038\/ncomms12082","journal-title":"Nat Commun"},{"key":"3736_CR71","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/0006-8993(90)91187-l","volume":"512","author":"M Shoji","year":"1990","unstructured":"Shoji M, Hirai S, Yamaguchi H et al (1990) Amyloid \u03b2-protein precursor accumulates in dystrophic neurites of senile plaques in Alzheimer-type dementia. Brain Res 512:164\u2013168. https:\/\/doi.org\/10.1016\/0006-8993(90)91187-l","journal-title":"Brain Res"},{"key":"3736_CR72","doi-asserted-by":"publisher","first-page":"7552","DOI":"10.1073\/pnas.88.17.7552","volume":"88","author":"P Cras","year":"1991","unstructured":"Cras P, Kawai M, Lowery D et al (1991) Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein. Proc Natl Acad Sci U S A 88:7552\u20137556. https:\/\/doi.org\/10.1073\/pnas.88.17.7552","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3736_CR73","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1111\/j.1460-9568.2009.07017.x","volume":"30","author":"X-M Zhang","year":"2009","unstructured":"Zhang X-M, Cai Y, Xiong K et al (2009) Beta-secretase-1 elevation in transgenic mouse models of Alzheimer\u2019s disease is associated with synaptic\/axonal pathology and amyloidogenesis: implications for neuritic plaque development. Eur J Neurosci 30:2271\u20132283. https:\/\/doi.org\/10.1111\/j.1460-9568.2009.07017.x","journal-title":"Eur J Neurosci"},{"key":"3736_CR74","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1111\/j.1460-9568.2010.07376.x","volume":"32","author":"Y Cai","year":"2010","unstructured":"Cai Y, Xiong K, Zhang X-M et al (2010) \u03b2-Secretase-1 elevation in aged monkey and Alzheimer\u2019s disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and \u03b2-amyloid accumulation. Eur J Neurosci 32:1223\u20131238. https:\/\/doi.org\/10.1111\/j.1460-9568.2010.07376.x","journal-title":"Eur J Neurosci"},{"key":"3736_CR75","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s00401-016-1558-9","volume":"132","author":"KR Sadleir","year":"2016","unstructured":"Sadleir KR, Kandalepas PC, Buggia-Pr\u00e9vot V et al (2016) Presynaptic dystrophic neurites surrounding amyloid plaques are sites of microtubule disruption, BACE1 elevation, and increased A\u03b2 generation in Alzheimer\u2019s disease. Acta Neuropathol 132:235\u2013256. https:\/\/doi.org\/10.1007\/s00401-016-1558-9","journal-title":"Acta Neuropathol"},{"key":"3736_CR76","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3233\/JAD-131400","volume":"38","author":"X-X Yan","year":"2014","unstructured":"Yan X-X, Ma C, Gai W-P et al (2014) Can BACE1 inhibition mitigate early axonal pathology in neurological diseases? J Alzheimers Dis 38:705\u2013718. https:\/\/doi.org\/10.3233\/JAD-131400","journal-title":"J Alzheimers Dis"},{"key":"3736_CR77","doi-asserted-by":"publisher","first-page":"E3699","DOI":"10.1073\/pnas.1510329112","volume":"112","author":"S Gowrishankar","year":"2015","unstructured":"Gowrishankar S, Yuan P, Wu Y et al (2015) Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer\u2019s disease amyloid plaques. Proc Natl Acad Sci U S A 112:E3699\u2013E3708. https:\/\/doi.org\/10.1073\/pnas.1510329112","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3736_CR78","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1097\/00005072-199704000-00001","volume":"56","author":"DW Dickson","year":"1997","unstructured":"Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56:321\u2013339. https:\/\/doi.org\/10.1097\/00005072-199704000-00001","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR79","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1097\/00005072-199507000-00009","volume":"54","author":"D Wang","year":"1995","unstructured":"Wang D, Munoz DG (1995) Qualitative and quantitative differences in senile plaque dystrophie neurites of Alzheimer\u02bcs disease and normal aged brain. J Neuropathol Exp Neurol 54:548\u2013556. https:\/\/doi.org\/10.1097\/00005072-199507000-00009","journal-title":"J Neuropathol Exp Neurol"},{"key":"3736_CR80","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s004010050920","volume":"96","author":"JH Su","year":"1998","unstructured":"Su JH, Cummings BJ, Cotman CW (1998) Plaque biogenesis in brain aging and Alzheimer\u2019s disease. II. Progressive transformation and developmental sequence of dystrophic neurites. Acta Neuropathol 96:463\u2013471. https:\/\/doi.org\/10.1007\/s004010050920","journal-title":"Acta Neuropathol"},{"key":"3736_CR81","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/j.1365-2990.2006.00756.x","volume":"32","author":"M Barrachina","year":"2006","unstructured":"Barrachina M, Maes T, Buesa C, Ferrer I (2006) Lysosome-associated membrane protein 1 (LAMP-1) in Alzheimer\u2019s disease. Neuropathol Appl Neurobiol 32:505\u2013516. https:\/\/doi.org\/10.1111\/j.1365-2990.2006.00756.x","journal-title":"Neuropathol Appl Neurobiol"},{"key":"3736_CR82","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1111\/ejn.13913","volume":"47","author":"S Hassiotis","year":"2018","unstructured":"Hassiotis S, Manavis J, Blumbergs PC et al (2018) Lysosomal LAMP1 immunoreactivity exists in both diffuse and neuritic amyloid plaques in the human hippocampus. Eur J Neurosci 47:1043\u20131053. https:\/\/doi.org\/10.1111\/ejn.13913","journal-title":"Eur J Neurosci"},{"key":"3736_CR83","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1038\/s41380-019-0396-2","volume":"24","author":"MG Sharoar","year":"2019","unstructured":"Sharoar MG, Hu X, Ma XM et al (2019) Sequential formation of different layers of dystrophic neurites in Alzheimer\u2019s brains. Mol Psychiatry 24:1369\u20131382. https:\/\/doi.org\/10.1038\/s41380-019-0396-2","journal-title":"Mol Psychiatry"},{"key":"3736_CR84","doi-asserted-by":"publisher","unstructured":"Sharoar MG, Palko S, Ge Y et al (2021) Accumulation of saposin in dystrophic neurites is linked to impaired lysosomal functions in Alzheimer\u2019s disease brains. Mol Neurodegener 16. https:\/\/doi.org\/10.1186\/s13024-021-00464-1","DOI":"10.1186\/s13024-021-00464-1"},{"key":"3736_CR85","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/s0014-4886(03)00252-8","volume":"184","author":"V Blanchard","year":"2003","unstructured":"Blanchard V, Moussaoui S, Czech C et al (2003) Time sequence of maturation of dystrophic neurites associated with A\u03b2 deposits in APP\/PS1 transgenic mice. Exp Neurol 184:247\u2013263. https:\/\/doi.org\/10.1016\/s0014-4886(03)00252-8","journal-title":"Exp Neurol"},{"key":"3736_CR86","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1006\/exnr.1998.7010","volume":"156","author":"TC Dickson","year":"1999","unstructured":"Dickson TC, King CE, McCormack GH, Vickers JC (1999) Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer\u2019s disease. Exp Neurol 156:100\u2013110. https:\/\/doi.org\/10.1006\/exnr.1998.7010","journal-title":"Exp Neurol"},{"key":"3736_CR87","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/0304-3940(88)90706-9","volume":"91","author":"C Duyckaerts","year":"1988","unstructured":"Duyckaerts C, Dela\u00e8re P, Poulain V et al (1988) Does amyloid precede paired helical filaments in the senile plaque? A study of 15 cases with graded intellectual status in aging and Alzheimer disease. Neurosci Lett 91:354\u2013359. https:\/\/doi.org\/10.1016\/0304-3940(88)90706-9","journal-title":"Neurosci Lett"},{"key":"3736_CR88","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/0304-3940(94)90608-4","volume":"171","author":"O Yasuhara","year":"1994","unstructured":"Yasuhara O, Kawamata T, Aimi Y et al (1994) Two types of dystrophic neurites in senile plaques of Alzheimer disease and elderly non-demented cases. Neurosci Lett 171:73\u201376. https:\/\/doi.org\/10.1016\/0304-3940(94)90608-4","journal-title":"Neurosci Lett"},{"key":"3736_CR89","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0006-8993(93)91595-j","volume":"619","author":"WC Benzing","year":"1993","unstructured":"Benzing WC, Brady DR, Mufson EJ, Armstrong DM (1993) Evidence that transmitter-containing dystrophic neurites precede those containing paired helical filaments within senile plaques in the entorhinal cortex of nondemented elderly and Alzheimer\u2019s disease patients. Brain Res 619:55\u201368. https:\/\/doi.org\/10.1016\/0006-8993(93)91595-j","journal-title":"Brain Res"},{"issue":"6","key":"3736_CR90","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.neurobiolaging.2007.09.003","volume":"30","author":"A Woodhouse","year":"2009","unstructured":"Woodhouse A, Vickers JC, Adlard PA, Dickson TC (2009) Dystrophic neurites in TgCRND8 and Tg2576 mice mimic human pathological brain aging. Neurobiol Aging 30(6):864\u2013874. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2007.09.003","journal-title":"Neurobiol Aging"},{"key":"3736_CR91","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1126\/science.1105681","volume":"307","author":"GB Stokin","year":"2005","unstructured":"Stokin GB, Lillo C, Falzone TL et al (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer\u2019s disease. Science 307:1282\u20131288. https:\/\/doi.org\/10.1126\/science.1105681","journal-title":"Science"},{"key":"3736_CR92","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/j.1365-2990.2012.01308.x","volume":"39","author":"R Adalbert","year":"2013","unstructured":"Adalbert R, Coleman MP (2013) Review: Axon pathology in age-related neurodegenerative disorders. Neuropathol Appl Neurobiol 39:90\u2013108. https:\/\/doi.org\/10.1111\/j.1365-2990.2012.01308.x","journal-title":"Neuropathol Appl Neurobiol"},{"key":"3736_CR93","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1097\/00001756-199209000-00012","volume":"3","author":"CJ Pike","year":"1992","unstructured":"Pike CJ, Cummings BJ, Cotman CW (1992) \u03b2-Amyloid induces neuritic dystrophy in vitro. Neuroreport 3:769\u2013772. https:\/\/doi.org\/10.1097\/00001756-199209000-00012","journal-title":"Neuroreport"},{"key":"3736_CR94","doi-asserted-by":"publisher","first-page":"5220","DOI":"10.1038\/s41467-021-25344-6","volume":"12","author":"R Bassil","year":"2021","unstructured":"Bassil R, Shields K, Granger K et al (2021) Improved modeling of human AD with an automated culturing platform for iPSC neurons, astrocytes and microglia. Nat Commun 12:5220. https:\/\/doi.org\/10.1038\/s41467-021-25344-6","journal-title":"Nat Commun"},{"key":"3736_CR95","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1073\/pnas.1017033108","volume":"108","author":"M Jin","year":"2011","unstructured":"Jin M, Shepardson N, Yang T et al (2011) Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci U S A 108:5819\u20135824. https:\/\/doi.org\/10.1073\/pnas.1017033108","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3736_CR96","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1038\/nm1782","volume":"14","author":"GM Shankar","year":"2008","unstructured":"Shankar GM, Li S, Mehta TH et al (2008) Amyloid-beta protein dimers isolated directly from Alzheimer\u2019s brains impair synaptic plasticity and memory. Nat Med 14:837\u2013842. https:\/\/doi.org\/10.1038\/nm1782","journal-title":"Nat Med"},{"key":"3736_CR97","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/nature06616","volume":"451","author":"M Meyer-Luehmann","year":"2008","unstructured":"Meyer-Luehmann M, Spires-Jones TL, Prada C et al (2008) Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer\u2019s disease. Nature 451:720\u2013724. https:\/\/doi.org\/10.1038\/nature06616","journal-title":"Nature"},{"key":"3736_CR98","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.ceca.2009.12.014","volume":"47","author":"C Supnet","year":"2010","unstructured":"Supnet C, Bezprozvanny I (2010) The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium 47:183\u2013189. https:\/\/doi.org\/10.1016\/j.ceca.2009.12.014","journal-title":"Cell Calcium"},{"key":"3736_CR99","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.neuron.2008.06.008","volume":"59","author":"KV Kuchibhotla","year":"2008","unstructured":"Kuchibhotla KV, Goldman ST, Lattarulo CR et al (2008) Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron 59:214\u2013225. https:\/\/doi.org\/10.1016\/j.neuron.2008.06.008","journal-title":"Neuron"},{"key":"3736_CR100","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41421-020-00233-2","volume":"7","author":"C Dias","year":"2021","unstructured":"Dias C, Nylandsted J (2021) Plasma membrane integrity in health and disease: significance and therapeutic potential. Cell Discov 7:4. https:\/\/doi.org\/10.1038\/s41421-020-00233-2","journal-title":"Cell Discov"},{"key":"3736_CR101","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1523\/JNEUROSCI.4456-09.2010","volume":"30","author":"H-Y Wu","year":"2010","unstructured":"Wu H-Y, Hudry E, Hashimoto T et al (2010) Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. J Neurosci 30:2636\u20132649. https:\/\/doi.org\/10.1523\/JNEUROSCI.4456-09.2010","journal-title":"J Neurosci"},{"key":"3736_CR102","doi-asserted-by":"crossref","unstructured":"Bai B, Vanderwall D, Li Y et al (2021) Proteomic landscape of Alzheimer\u2019s disease: novel insights into pathogenesis and biomarker discovery. Mol Neurodegener 16","DOI":"10.1186\/s13024-021-00474-z"},{"key":"3736_CR103","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/s41593-021-00999-y","volume":"25","author":"ECB Johnson","year":"2022","unstructured":"Johnson ECB, Carter EK, Dammer EB et al (2022) Large-scale deep multi-layer analysis of Alzheimer\u2019s disease brain reveals strong proteomic disease-related changes not observed at the RNA level. Nat Neurosci 25:213\u2013225. https:\/\/doi.org\/10.1038\/s41593-021-00999-y","journal-title":"Nat Neurosci"},{"key":"3736_CR104","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13024-018-0282-4","volume":"13","author":"ECB Johnson","year":"2018","unstructured":"Johnson ECB, Dammer EB, Duong DM et al (2018) Deep proteomic network analysis of Alzheimer\u2019s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease. Mol Neurodegener 13:52. https:\/\/doi.org\/10.1186\/s13024-018-0282-4","journal-title":"Mol Neurodegener"},{"key":"3736_CR105","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/BF03033772","volume":"7","author":"A Woodhouse","year":"2005","unstructured":"Woodhouse A, West AK, Chuckowree JA et al (2005) Does beta-amyloid plaque formation cause structural injury to neuronal processes? Neurotox Res 7:5\u201315. https:\/\/doi.org\/10.1007\/BF03033772","journal-title":"Neurotox Res"},{"key":"3736_CR106","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1046\/j.1440-1681.2000.03292.x","volume":"27","author":"C King","year":"2000","unstructured":"King C, Adlard P, Dickson T, Vickers J (2000) Neuronal response to physical injury and its relationship to the pathology of Alzheimer\u2019s disease. Clin Exp Pharmacol Physiol 27:548\u2013552. https:\/\/doi.org\/10.1046\/j.1440-1681.2000.03292.x","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"3736_CR107","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/s0002-9440(10)64700-1","volume":"156","author":"GK Gouras","year":"2000","unstructured":"Gouras GK, Tsai J, Naslund J et al (2000) Intraneuronal Abeta42 accumulation in human brain. Am J Pathol 156:15\u201320. https:\/\/doi.org\/10.1016\/s0002-9440(10)64700-1","journal-title":"Am J Pathol"},{"key":"3736_CR108","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1016\/s0002-9440(10)64463-x","volume":"161","author":"RH Takahashi","year":"2002","unstructured":"Takahashi RH, Milner TA, Li F et al (2002) Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161:1869\u20131879. https:\/\/doi.org\/10.1016\/s0002-9440(10)64463-x","journal-title":"Am J Pathol"},{"key":"3736_CR109","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/pin.12520","volume":"67","author":"RH Takahashi","year":"2017","unstructured":"Takahashi RH, Nagao T, Gouras GK (2017) Plaque formation and the intraneuronal accumulation of \u03b2-amyloid in Alzheimer\u2019s disease. Pathol Int 67:185\u2013193. https:\/\/doi.org\/10.1111\/pin.12520","journal-title":"Pathol Int"},{"key":"3736_CR110","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/s41593-022-01084-8","volume":"25","author":"J-H Lee","year":"2022","unstructured":"Lee J-H, Yang D-S, Goulbourne CN et al (2022) Faulty autolysosome acidification in Alzheimer\u2019s disease mouse models induces autophagic build-up of A\u03b2 in neurons, yielding senile plaques. Nat Neurosci 25:688\u2013701. https:\/\/doi.org\/10.1038\/s41593-022-01084-8","journal-title":"Nat Neurosci"},{"key":"3736_CR111","doi-asserted-by":"publisher","first-page":"196.e29","DOI":"10.1016\/j.neurobiolaging.2010.05.027","volume":"33","author":"S Jawhar","year":"2012","unstructured":"Jawhar S, Trawicka A, Jenneckens C et al (2012) Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal A\u03b2 aggregation in the 5XFAD mouse model of Alzheimer\u2019s disease. Neurobiol Aging 33:196.e29-196.e40. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2010.05.027","journal-title":"Neurobiol Aging"},{"key":"3736_CR112","doi-asserted-by":"publisher","first-page":"3647","DOI":"10.1016\/j.celrep.2018.11.095","volume":"25","author":"COY Hung","year":"2018","unstructured":"Hung COY, Livesey FJ (2018) Altered \u03b3-secretase processing of APP disrupts lysosome and autophagosome function in monogenic Alzheimer\u2019s disease. Cell Rep 25:3647-3660.e2. https:\/\/doi.org\/10.1016\/j.celrep.2018.11.095","journal-title":"Cell Rep"},{"key":"3736_CR113","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s00401-016-1577-6","volume":"132","author":"I Lauritzen","year":"2016","unstructured":"Lauritzen I, Pardossi-Piquard R, Bourgeois A et al (2016) Intraneuronal aggregation of the \u03b2-CTF fragment of APP (C99) induces A\u03b2-independent lysosomal-autophagic pathology. Acta Neuropathol 132:257\u2013276. https:\/\/doi.org\/10.1007\/s00401-016-1577-6","journal-title":"Acta Neuropathol"},{"key":"3736_CR114","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.neurobiolaging.2015.11.013","volume":"39","author":"Y Jiang","year":"2016","unstructured":"Jiang Y, Rigoglioso A, Peterhoff CM et al (2016) Partial BACE1 reduction in a Down syndrome mouse model blocks Alzheimer-related endosomal anomalies and cholinergic neurodegeneration: role of APP-CTF. Neurobiol Aging 39:90\u201398. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2015.11.013","journal-title":"Neurobiol Aging"},{"key":"3736_CR115","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1016\/j.celrep.2015.07.050","volume":"12","author":"J-H Lee","year":"2015","unstructured":"Lee J-H, McBrayer MK, Wolfe DM et al (2015) Presenilin 1 maintains lysosomal Ca(2+) homeostasis via TRPML1 by regulating vATPase-mediated lysosome acidification. Cell Rep 12:1430\u20131444. https:\/\/doi.org\/10.1016\/j.celrep.2015.07.050","journal-title":"Cell Rep"},{"key":"3736_CR116","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/j.cell.2010.05.008","volume":"141","author":"J-H Lee","year":"2010","unstructured":"Lee J-H, Yu WH, Kumar A et al (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146\u20131158. https:\/\/doi.org\/10.1016\/j.cell.2010.05.008","journal-title":"Cell"},{"key":"3736_CR117","doi-asserted-by":"publisher","first-page":"eabj5716","DOI":"10.1126\/sciadv.abj5716","volume":"8","author":"PPY Lie","year":"2022","unstructured":"Lie PPY, Yoo L, Goulbourne CN et al (2022) Axonal transport of late endosomes and amphisomes is selectively modulated by local Ca(2+) efflux and disrupted by PSEN1 loss of function. Sci Adv 8:eabj5716. https:\/\/doi.org\/10.1126\/sciadv.abj5716","journal-title":"Sci Adv"},{"key":"3736_CR118","doi-asserted-by":"publisher","first-page":"7817","DOI":"10.1523\/JNEUROSCI.6412-10.2011","volume":"31","author":"S Lee","year":"2011","unstructured":"Lee S, Sato Y, Nixon RA (2011) Lysosomal proteolysis inhibition selectively disrupts axonal transport of degradative organelles and causes an Alzheimer\u2019s-like axonal dystrophy. J Neurosci 31:7817\u20137830. https:\/\/doi.org\/10.1523\/JNEUROSCI.6412-10.2011","journal-title":"J Neurosci"},{"key":"3736_CR119","doi-asserted-by":"publisher","first-page":"879","DOI":"10.3233\/jad-2009-1010","volume":"16","author":"S Altamura","year":"2009","unstructured":"Altamura S, Muckenthaler MU (2009) Iron toxicity in diseases of aging: Alzheimer\u2019s disease, Parkinson\u2019s disease and atherosclerosis. J Alzheimer\u2019s Dis 16:879\u2013895. https:\/\/doi.org\/10.3233\/jad-2009-1010","journal-title":"J Alzheimer\u2019s Dis"},{"key":"3736_CR120","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3233\/JAD-2010-1239","volume":"19","author":"MA Smith","year":"2010","unstructured":"Smith MA, Zhu X, Tabaton M et al (2010) Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J Alzheimers Dis 19:363\u2013372. https:\/\/doi.org\/10.3233\/JAD-2010-1239","journal-title":"J Alzheimers Dis"},{"key":"3736_CR121","doi-asserted-by":"publisher","first-page":"S379","DOI":"10.3233\/jad-179944","volume":"64","author":"DJR Lane","year":"2018","unstructured":"Lane DJR, Ayton S, Bush AI (2018) Iron and Alzheimer\u2019s disease: an update on emerging mechanisms. J Alzheimer\u2019s Dis 64:S379\u2013S395. https:\/\/doi.org\/10.3233\/jad-179944","journal-title":"J Alzheimer\u2019s Dis"},{"key":"3736_CR122","doi-asserted-by":"publisher","first-page":"5848","DOI":"10.1523\/JNEUROSCI.22-14-05848.2002","volume":"22","author":"GJ Kress","year":"2002","unstructured":"Kress GJ, Dineley KE, Reynolds IJ (2002) The relationship between intracellular free iron and cell injury in cultured neurons, astrocytes, and oligodendrocytes. J Neurosci 22:5848\u20135855. https:\/\/doi.org\/10.1523\/JNEUROSCI.22-14-05848.2002","journal-title":"J Neurosci"},{"key":"3736_CR123","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1002\/glia.20678","volume":"56","author":"KO Lopes","year":"2008","unstructured":"Lopes KO, Sparks DL, Streit WJ (2008) Microglial dystrophy in the aged and Alzheimer\u2019s disease brain is associated with ferritin immunoreactivity. Glia 56:1048\u20131060. https:\/\/doi.org\/10.1002\/glia.20678","journal-title":"Glia"},{"key":"3736_CR124","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.3233\/jad-215334","volume":"85","author":"WJ Streit","year":"2022","unstructured":"Streit WJ, Rotter J, Winter K et al (2022) Droplet degeneration of hippocampal and cortical neurons signifies the beginning of neuritic plaque formation. J Alzheimer\u2019s Dis 85:1701\u20131720. https:\/\/doi.org\/10.3233\/jad-215334","journal-title":"J Alzheimer\u2019s Dis"},{"key":"3736_CR125","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/jnr.10661","volume":"73","author":"GM Bishop","year":"2003","unstructured":"Bishop GM, Robinson SR (2003) Human A?1-42 reduces iron-induced toxicity in rat cerebral cortex. J Neurosci Res 73:316\u2013323. https:\/\/doi.org\/10.1002\/jnr.10661","journal-title":"J Neurosci Res"},{"key":"3736_CR126","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40478-022-01324-9","volume":"10","author":"JM Walker","year":"2022","unstructured":"Walker JM, Kazempour Dehkordi S, Fracassi A et al (2022) Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling. Acta Neuropathol Commun 10:23. https:\/\/doi.org\/10.1186\/s40478-022-01324-9","journal-title":"Acta Neuropathol Commun"},{"key":"3736_CR127","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.neurobiolaging.2019.06.009","volume":"82","author":"GK Hansra","year":"2019","unstructured":"Hansra GK, Popov G, Banaczek PO et al (2019) The neuritic plaque in Alzheimer\u2019s disease: perivascular degeneration of neuronal processes. Neurobiol Aging 82:88\u2013101. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2019.06.009","journal-title":"Neurobiol Aging"},{"key":"3736_CR128","first-page":"1167","volume":"140","author":"DG Munoz","year":"1992","unstructured":"Munoz DG, Wang D (1992) Tangle-associated neuritic clusters. A new lesion in Alzheimer\u2019s disease and aging suggests that aggregates of dystrophic neurites are not necessarily associated with beta\/A4. Am J Pathol 140:1167","journal-title":"Am J Pathol"},{"key":"3736_CR129","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-12679-1_1","volume":"215","author":"H Braak","year":"2015","unstructured":"Braak H, Del Tredici K (2015) Neuroanatomy and pathology of sporadic Alzheimer\u2019s disease. Adv Anat Embryol Cell Biol 215:1\u2013162","journal-title":"Adv Anat Embryol Cell Biol"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03736-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-023-03736-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03736-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T01:29:09Z","timestamp":1713922149000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-023-03736-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,8]]},"references-count":129,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["3736"],"URL":"https:\/\/doi.org\/10.1007\/s12035-023-03736-7","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,8]]},"assertion":[{"value":"21 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This review article uses images of tissue sections from postmortem tissue specimens from the University of Florida Human Brain and Tissue Bank. Approval for scientific use of these specimens was granted by the Internal Review Board of the University of Florida.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The authors affirm that human research participants provided informed consent for donation of tissue specimens to the University of Florida Human Brain and Tissue Bank.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The authors affirm that human research participants provided informed consent for publication of the images used in the manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}