{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:53:39Z","timestamp":1782852819095,"version":"3.54.5"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["435819"],"award-info":[{"award-number":["435819"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"crossref","award":["418489"],"award-info":[{"award-number":["418489"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["126127"],"award-info":[{"award-number":["126127"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015569","name":"Canadian Consortium on Neurodegeneration in Aging","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015569","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Canadian Foundation for Innovation","award":["34213"],"award-info":[{"award-number":["34213"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1007\/s12035-021-02476-w","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T07:10:34Z","timestamp":1625641834000},"page":"5014-5030","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Precocious White Matter Inflammation and Behavioural Inflexibility Precede Learning and Memory Impairment in the TgAPP21 Rat Model of Alzheimer Disease"],"prefix":"10.1007","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2921-4339","authenticated-orcid":false,"given":"Alexander","family":"Levit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Hough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngkyung","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9883-3291","authenticated-orcid":false,"given":"Yuksel","family":"Agca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-7448","authenticated-orcid":false,"given":"Cansu","family":"Agca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0487-734X","authenticated-orcid":false,"given":"Vladimir","family":"Hachinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-2019","authenticated-orcid":false,"given":"Brian L.","family":"Allman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4728-8067","authenticated-orcid":false,"given":"Shawn N.","family":"Whitehead","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,7]]},"reference":[{"key":"2476_CR1","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1093\/gerona\/62.10.1134","volume":"62","author":"JK Johnson","year":"2007","unstructured":"Johnson JK, Lui LY, Yaffe K (2007) Executive function, more than global cognition, predicts functional decline and mortality in elderly women. J Gerontol - Ser A Biol Sci Med Sci 62:1134\u20131141. https:\/\/doi.org\/10.1093\/gerona\/62.10.1134","journal-title":"J Gerontol - Ser A Biol Sci Med Sci"},{"key":"2476_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1146\/annurev-psych-113011-143750","volume":"64","author":"A Diamond","year":"2013","unstructured":"Diamond A (2013) Executive functions. Annu Rev Psychol 64:135\u2013141. https:\/\/doi.org\/10.1146\/annurev-psych-113011-143750","journal-title":"Annu Rev Psychol"},{"key":"2476_CR3","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.cger.2013.07.002","volume":"29","author":"CN Harada","year":"2013","unstructured":"Harada CN, Natelson Love MC, Triebel KL (2013) Normal cognitive aging. Clin Geriatr Med 29:737\u2013752. https:\/\/doi.org\/10.1016\/j.cger.2013.07.002","journal-title":"Clin Geriatr Med"},{"key":"2476_CR4","first-page":"226","volume":"28","author":"SM Grieve","year":"2007","unstructured":"Grieve SM, Williams LM, Paul RH et al (2007) Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study. Am J Neuroradiol 28:226\u2013235","journal-title":"Am J Neuroradiol"},{"key":"2476_CR5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nrn1323","volume":"5","author":"T Hedden","year":"2004","unstructured":"Hedden T, Gabrieli JDE (2004) Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci 5:87\u201396. https:\/\/doi.org\/10.1038\/nrn1323","journal-title":"Nat Rev Neurosci"},{"key":"2476_CR6","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1093\/cercor\/bhy031","volume":"29","author":"JS Rabin","year":"2018","unstructured":"Rabin JS, Perea RD, Buckley RF et al (2018) Global white matter diffusion characteristics predict longitudinal cognitive change independently of amyloid status in clinically normal older adults. Cereb Cortex 29:1251\u20131262. https:\/\/doi.org\/10.1093\/cercor\/bhy031","journal-title":"Cereb Cortex"},{"key":"2476_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2013.00032","volume":"7","author":"E Sasson","year":"2013","unstructured":"Sasson E, Doniger GM, Pasternak O et al (2013) White matter correlates of cognitive domains in normal aging with diffusion tensor imaging. Front Neurosci 7:1\u201313. https:\/\/doi.org\/10.3389\/fnins.2013.00032","journal-title":"Front Neurosci"},{"key":"2476_CR8","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1037\/0894-4105.14.2.224","volume":"14","author":"FM Gunning-Dixon","year":"2000","unstructured":"Gunning-Dixon FM, Raz N (2000) The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology 14:224\u2013232. https:\/\/doi.org\/10.1037\/0894-4105.14.2.224","journal-title":"Neuropsychology"},{"key":"2476_CR9","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.4.972","author":"CR Guttmann","year":"1998","unstructured":"Guttmann CR, Jolesz FA, Kikinis R et al (1998) White matter changes with normal aging. Neurology. https:\/\/doi.org\/10.1212\/WNL.50.4.972","journal-title":"Neurology"},{"key":"2476_CR10","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1177\/0271678X17713105","volume":"38","author":"JH Fowler","year":"2018","unstructured":"Fowler JH, McQueen J, Holland PR et al (2018) Dimethyl fumarate improves white matter function following severe hypoperfusion: involvement of microglia\/macrophages and inflammatory mediators. J Cereb Blood Flow Metab 38:1354\u20131370. https:\/\/doi.org\/10.1177\/0271678X17713105","journal-title":"J Cereb Blood Flow Metab"},{"key":"2476_CR11","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1111\/jnc.14271","volume":"144","author":"Y Hase","year":"2018","unstructured":"Hase Y, Horsburgh K, Ihara M, Kalaria RN (2018) White matter degeneration in vascular and other ageing-related dementias. J Neurochem 144:617\u2013633. https:\/\/doi.org\/10.1111\/jnc.14271","journal-title":"J Neurochem"},{"key":"2476_CR12","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1111\/cns.12374","volume":"21","author":"LF Lan","year":"2015","unstructured":"Lan LF, Zheng L, Yang X et al (2015) Peroxisome proliferator-activated receptor-\u03b3 agonist pioglitazone ameliorates white matter lesion and cognitive impairment in hypertensive rats. CNS Neurosci Ther 21:410\u2013416. https:\/\/doi.org\/10.1111\/cns.12374","journal-title":"CNS Neurosci Ther"},{"key":"2476_CR13","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1002\/glia.23190","volume":"66","author":"Y Manso","year":"2018","unstructured":"Manso Y, Holland PR, Kitamura A et al (2018) Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease. Glia 66:34\u201346. https:\/\/doi.org\/10.1002\/glia.23190","journal-title":"Glia"},{"key":"2476_CR14","doi-asserted-by":"publisher","unstructured":"Miyanohara J, Kakae M, Nagayasu K, et al (2018) TRPM2 channel aggravates CNS inflammation and cognitive impairment via activation of microglia in chronic cerebral hypoperfusion. J Neurosci 2451\u201317.https:\/\/doi.org\/10.1523\/JNEUROSCI.2451-17.2018","DOI":"10.1523\/JNEUROSCI.2451-17.2018"},{"key":"2476_CR15","doi-asserted-by":"publisher","first-page":"3336","DOI":"10.1161\/STROKEAHA.117.018505","volume":"48","author":"C Qin","year":"2017","unstructured":"Qin C, Fan WH, Liu Q et al (2017) Fingolimod protects against ischemic white matter damage by modulating microglia toward M2 polarization via STAT3 pathway. Stroke 48:3336\u20133346. https:\/\/doi.org\/10.1161\/STROKEAHA.117.018505","journal-title":"Stroke"},{"key":"2476_CR16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s11357-017-9965-y","volume":"39","author":"E Shobin","year":"2017","unstructured":"Shobin E, Bowley MP, Estrada LI et al (2017) Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey. GeroScience 39:199\u2013220. https:\/\/doi.org\/10.1007\/s11357-017-9965-y","journal-title":"GeroScience"},{"key":"2476_CR17","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3389\/fnagi.2017.00191","volume":"9","author":"G Wolf","year":"2017","unstructured":"Wolf G, Lotan A, Lifschytz T et al (2017) Differentially severe cognitive effects of compromised cerebral blood flow in aged mice: association with myelin degradation and microglia activation. Front Aging Neurosci 9:191. https:\/\/doi.org\/10.3389\/fnagi.2017.00191","journal-title":"Front Aging Neurosci"},{"key":"2476_CR18","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s40478-014-0142-6","volume":"2","author":"WJ Streit","year":"2014","unstructured":"Streit WJ, Xue Q-S, Tischer J, Bechmann I (2014) Microglial pathology. Acta Neuropathol Commun 2:142. https:\/\/doi.org\/10.1186\/s40478-014-0142-6","journal-title":"Acta Neuropathol Commun"},{"key":"2476_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnmol.2017.00206","volume":"10","author":"D Raj","year":"2017","unstructured":"Raj D, Yin Z, Breur M et al (2017) Increased white matter inflammation in aging- and Alzheimer\u2019s disease brain. Front Mol Neurosci 10:1\u201318. https:\/\/doi.org\/10.3389\/fnmol.2017.00206","journal-title":"Front Mol Neurosci"},{"key":"2476_CR20","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1001\/jama.2015.4668","volume":"313","author":"WJ Jansen","year":"2015","unstructured":"Jansen WJ, Ossenkoppele R, Knol DL et al (2015) Prevalence of cerebral amyloid pathology in persons without dementia. JAMA 313:1924. https:\/\/doi.org\/10.1001\/jama.2015.4668","journal-title":"JAMA"},{"key":"2476_CR21","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","journal-title":"Acta Neuropathol"},{"key":"2476_CR22","doi-asserted-by":"crossref","unstructured":"von Bernhardi R, Eugen\u00edn-von Bernhardi L, Eugen\u00edn J (2015) Microglial cell dysregulation in brain aging and neurodegeneration. Front Aging Neurosci 7","DOI":"10.3389\/fnagi.2015.00124"},{"key":"2476_CR23","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.neurobiolaging.2012.09.012","volume":"34","author":"TL Sudduth","year":"2013","unstructured":"Sudduth TL, Schmitt FA, Nelson PT, Wilcock DM (2013) Neuroinflammatory phenotype in early Alzheimer\u2019s disease. Neurobiol Aging 34:1051\u20131059. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2012.09.012","journal-title":"Neurobiol Aging"},{"key":"2476_CR24","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1002\/ana.24647","volume":"79","author":"S Lee","year":"2016","unstructured":"Lee S, Viqar F, Zimmerman ME et al (2016) White matter hyperintensities are a core feature of Alzheimer\u2019s disease: evidence from the dominantly inherited Alzheimer network. Ann Neurol 79:929\u2013939. https:\/\/doi.org\/10.1002\/ana.24647","journal-title":"Ann Neurol"},{"key":"2476_CR25","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jalz.2014.04.518","volume":"11","author":"KH Maier-Hein","year":"2015","unstructured":"Maier-Hein KH, Westin CF, Shenton ME et al (2015) Widespread white matter degeneration preceding the onset of dementia. Alzheimer\u2019s Dement 11:485-493.e2. https:\/\/doi.org\/10.1016\/j.jalz.2014.04.518","journal-title":"Alzheimer\u2019s Dement"},{"key":"2476_CR26","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.acn.2005.07.002","volume":"21","author":"S Baudic","year":"2006","unstructured":"Baudic S, Barba GD, Thibaudet MC et al (2006) Executive function deficits in early Alzheimer\u2019s disease and their relations with episodic memory. Arch Clin Neuropsychol 21:15\u201321. https:\/\/doi.org\/10.1016\/j.acn.2005.07.002","journal-title":"Arch Clin Neuropsychol"},{"key":"2476_CR27","doi-asserted-by":"publisher","first-page":"S375","DOI":"10.3233\/JAD-141470","volume":"42","author":"S Belleville","year":"2014","unstructured":"Belleville S, Fouquet C, Duchesne S et al (2014) Detecting early preclinical alzheimer\u2019s disease via cognition, neuropsychiatry, and neuroimaging: qualitative review and recommendations for testing. J Alzheimer\u2019s Dis 42:S375\u2013S382","journal-title":"J Alzheimer\u2019s Dis"},{"key":"2476_CR28","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/brain\/121.1.135","volume":"121","author":"C Fabrigoule","year":"1998","unstructured":"Fabrigoule C, Rouch I, Taberly A et al (1998) Cognitive process in preclinical phase of dementia. Brain 121:135\u2013141. https:\/\/doi.org\/10.1093\/brain\/121.1.135","journal-title":"Brain"},{"key":"2476_CR29","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1017\/S1355617708080302","volume":"14","author":"E Grober","year":"2008","unstructured":"Grober E, Hall CB, Lipton RB et al (2008) Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer\u2019s disease. J Int Neuropsychol Soc 14:266\u2013278. https:\/\/doi.org\/10.1017\/S1355617708080302","journal-title":"J Int Neuropsychol Soc"},{"key":"2476_CR30","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1471-2202-9-28","volume":"9","author":"C Agca","year":"2008","unstructured":"Agca C, Fritz JJ, Walker LC et al (2008) Development of transgenic rats producing human \u03b2-amyloid precursor protein as a model for Alzheimer\u2019s disease: transgene and endogenous APP genes are regulated tissue-specifically. BMC Neurosci 9:28. https:\/\/doi.org\/10.1186\/1471-2202-9-28","journal-title":"BMC Neurosci"},{"key":"2476_CR31","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1111\/j.1471-4159.2011.07551.x","volume":"120","author":"RF Rosen","year":"2012","unstructured":"Rosen RF, Fritz JJ, Dooyema J et al (2012) Exogenous seeding of cerebral beta-amyloid deposition in betaAPP-transgenic rats. J Neurochem 120:660\u2013666. https:\/\/doi.org\/10.1111\/j.1471-4159.2011.07551.x","journal-title":"J Neurochem"},{"key":"2476_CR32","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/2045-8118-12-2","volume":"12","author":"GD Silverberg","year":"2015","unstructured":"Silverberg GD, Miller MC, Pascale CL et al (2015) Kaolin-induced chronic hydrocephalus accelerates amyloid deposition and vascular disease in transgenic rats expressing high levels of human APP. Fluids Barriers CNS 12:2. https:\/\/doi.org\/10.1186\/2045-8118-12-2","journal-title":"Fluids Barriers CNS"},{"key":"2476_CR33","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.bbr.2017.07.006","volume":"333","author":"A Levit","year":"2017","unstructured":"Levit A, Regis AM, Garabon JR et al (2017) Behavioural inflexibility in a comorbid rat model of striatal ischemic injury and mutant hAPP overexpression. Behav Brain Res 333:267\u2013275. https:\/\/doi.org\/10.1016\/j.bbr.2017.07.006","journal-title":"Behav Brain Res"},{"key":"2476_CR34","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.bbi.2019.02.013","volume":"80","author":"A Levit","year":"2019","unstructured":"Levit A, Regis AMAM, Gibson A et al (2019) Impaired behavioural flexibility related to white matter microgliosis in the TgAPP21 rat model of Alzheimer disease. Brain Behav Immun 80:25\u201334. https:\/\/doi.org\/10.1016\/j.bbi.2019.02.013","journal-title":"Brain Behav Immun"},{"key":"2476_CR35","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.bbr.2008.02.008","volume":"190","author":"SB Floresco","year":"2008","unstructured":"Floresco SB, Block AE, Tse MTL (2008) Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure. Behav Brain Res 190:85\u201396. https:\/\/doi.org\/10.1016\/j.bbr.2008.02.008","journal-title":"Behav Brain Res"},{"key":"2476_CR36","doi-asserted-by":"publisher","unstructured":"Brady AM, Floresco SB (2015) Operant procedures for assessing behavioral flexibility in rats. J Vis Exp e52387. https:\/\/doi.org\/10.3791\/52387","DOI":"10.3791\/52387"},{"key":"2476_CR37","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1161\/hs1101.097397","volume":"32","author":"RL Roof","year":"2001","unstructured":"Roof RL, Schielke GP, Ren X, Hall ED (2001) A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats. Stroke 32:2648\u20132657","journal-title":"Stroke"},{"key":"2476_CR38","doi-asserted-by":"publisher","unstructured":"Wong WT (2013) Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation. Front Cell Neurosci 7. https:\/\/doi.org\/10.3389\/fncel.2013.00022","DOI":"10.3389\/fncel.2013.00022"},{"key":"2476_CR39","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","volume":"119","author":"MV Sofroniew","year":"2010","unstructured":"Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7\u201335. https:\/\/doi.org\/10.1007\/s00401-009-0619-8","journal-title":"Acta Neuropathol"},{"key":"2476_CR40","volume-title":"The rat brain in stereotaxic coordinates","author":"G Paxinos","year":"2007","unstructured":"Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press\/Elsevier, , Amsterdam","edition":"6"},{"key":"2476_CR41","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/J.BBAGEN.2018.03.011","volume":"1862","author":"S Caughlin","year":"2018","unstructured":"Caughlin S, Maheshwari S, Agca Y et al (2018) Membrane-lipid homeostasis in a prodromal rat model of Alzheimer\u2019s disease: characteristic profiles in ganglioside distributions during aging detected using MALDI imaging mass spectrometry. Biochim Biophys Acta - Gen Subj 1862:1327\u20131338. https:\/\/doi.org\/10.1016\/J.BBAGEN.2018.03.011","journal-title":"Biochim Biophys Acta - Gen Subj"},{"key":"2476_CR42","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/1471-2105-7-123","volume":"7","author":"HJ Motulsky","year":"2006","unstructured":"Motulsky HJ, Brown RE (2006) Detecting outliers when fitting data with nonlinear regression\u2014a new method based on robust nonlinear regression and the false discovery rate. BMC Bioinformatics 7:123. https:\/\/doi.org\/10.1186\/1471-2105-7-123","journal-title":"BMC Bioinformatics"},{"key":"2476_CR43","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1093\/cercor\/bhh003","volume":"14","author":"D Head","year":"2004","unstructured":"Head D, Buckner RL, Shimony JS et al (2004) Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the alzheimer type: evidence from diffusion tensor imaging. Cereb Cortex 14:410\u2013423. https:\/\/doi.org\/10.1093\/cercor\/bhh003","journal-title":"Cereb Cortex"},{"key":"2476_CR44","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1017\/S1355617712000045","volume":"18","author":"EJ Marco","year":"2012","unstructured":"Marco EJ, Harrell KM, Brown WS et al (2012) Processing speed delays contribute to executive function deficits in individuals with agenesis of the corpus callosum. J Int Neuropsychol Soc 18:521\u2013529. https:\/\/doi.org\/10.1017\/S1355617712000045","journal-title":"J Int Neuropsychol Soc"},{"key":"2476_CR45","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.jocn.2017.05.032","volume":"43","author":"A Papathanasiou","year":"2017","unstructured":"Papathanasiou A, Messinis L, Zampakis P, Papathanasopoulos P (2017) Corpus callosum atrophy as a marker of clinically meaningful cognitive decline in secondary progressive multiple sclerosis. Impact on employment status. J Clin Neurosci 43:170\u2013175. https:\/\/doi.org\/10.1016\/j.jocn.2017.05.032","journal-title":"J Clin Neurosci"},{"key":"2476_CR46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104549","volume":"9","author":"MB Moreno","year":"2014","unstructured":"Moreno MB, Concha L, Gonz\u00e1lez-Santos L et al (2014) Correlation between corpus callosum sub-segmental area and cognitive processes in school-age children. PLoS One 9:e104549. https:\/\/doi.org\/10.1371\/journal.pone.0104549","journal-title":"PLoS One"},{"key":"2476_CR47","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.neuroscience.2013.12.019","volume":"276","author":"S Treit","year":"2014","unstructured":"Treit S, Chen Z, Rasmussen C, Beaulieu C (2014) White matter correlates of cognitive inhibition during development: a diffusion tensor imaging study. Neuroscience 276:87\u201397. https:\/\/doi.org\/10.1016\/j.neuroscience.2013.12.019","journal-title":"Neuroscience"},{"key":"2476_CR48","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3389\/fpsyg.2018.00118","volume":"9","author":"PC Mamiya","year":"2018","unstructured":"Mamiya PC, Richards TL, Kuhl PK (2018) Right forceps minor and anterior thalamic radiation predict executive function skills in young bilingual adults. Front Psychol 9:118. https:\/\/doi.org\/10.3389\/fpsyg.2018.00118","journal-title":"Front Psychol"},{"key":"2476_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2051-5960-2-1","volume":"2","author":"LE Collins-Praino","year":"2014","unstructured":"Collins-Praino LE, Francis YI, Griffith EY et al (2014) Soluble amyloid beta levels are elevated in the white matter of Alzheimer\u2019s patients, independent of cortical plaque severity. Acta Neuropathol Commun 2:1\u201310","journal-title":"Acta Neuropathol Commun"},{"key":"2476_CR50","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41593-018-0290-2","volume":"22","author":"C B\u00f6ttcher","year":"2019","unstructured":"B\u00f6ttcher C, Schlickeiser S, Sneeboer MAM et al (2019) Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. Nat Neurosci 22:78\u201390. https:\/\/doi.org\/10.1038\/s41593-018-0290-2","journal-title":"Nat Neurosci"},{"key":"2476_CR51","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.celrep.2020.01.010","volume":"30","author":"T Masuda","year":"2020","unstructured":"Masuda T, Sankowski R, Staszewski O, Prinz M (2020) Microglia heterogeneity in the single-cell era. Cell Rep 30:1271\u20131281","journal-title":"Cell Rep"},{"key":"2476_CR52","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/s41380-019-0609-8","volume":"25","author":"YL Tan","year":"2020","unstructured":"Tan YL, Yuan Y, Tian L (2020) Microglial regional heterogeneity and its role in the brain. Mol Psychiatry 25:351\u2013367","journal-title":"Mol Psychiatry"},{"key":"2476_CR53","doi-asserted-by":"crossref","unstructured":"Cohen J, Torres C (2019) Astrocyte senescence: evidence and significance. Aging Cell 18","DOI":"10.1111\/acel.12937"},{"key":"2476_CR54","unstructured":"Palmer AL, Ousman SS (2018) Astrocytes and aging. Front. Aging Neurosci 10"},{"key":"2476_CR55","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1016\/j.neubiorev.2012.02.011","volume":"36","author":"R Lalonde","year":"2012","unstructured":"Lalonde R, Fukuchi K, Strazielle C (2012) APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD). Neurosci Biobehav Rev 36:1357\u20131375. https:\/\/doi.org\/10.1016\/j.neubiorev.2012.02.011","journal-title":"Neurosci Biobehav Rev"},{"key":"2476_CR56","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.brainres.2019.05.031","volume":"1719","author":"CA Toro","year":"2019","unstructured":"Toro CA, Zhang L, Cao J, Cai D (2019) Sex differences in Alzheimer\u2019s disease\u2014understanding the molecular impact. Brain Res 1719:194\u2013207. https:\/\/doi.org\/10.1016\/j.brainres.2019.05.031","journal-title":"Brain Res"},{"key":"2476_CR57","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/s42003-021-02259-y","volume":"4","author":"M-V Guillot-Sestier","year":"2021","unstructured":"Guillot-Sestier M-V, Araiz AR, Mela V et al (2021) Microglial metabolism is a pivotal factor in sexual dimorphism in Alzheimer\u2019s disease. Commun Biol 4:711. https:\/\/doi.org\/10.1038\/s42003-021-02259-y","journal-title":"Commun Biol"},{"key":"2476_CR58","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s12868-016-0281-8","volume":"17","author":"C Agca","year":"2016","unstructured":"Agca C, Klakotskaia D, Schachtman TR et al (2016) Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention. BMC Neurosci 17:46. https:\/\/doi.org\/10.1186\/s12868-016-0281-8","journal-title":"BMC Neurosci"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-021-02476-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-021-02476-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-021-02476-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T04:04:55Z","timestamp":1672718695000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-021-02476-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,7]]},"references-count":58,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["2476"],"URL":"https:\/\/doi.org\/10.1007\/s12035-021-02476-w","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,7]]},"assertion":[{"value":"4 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal ethics and procedures were approved by the Animal Care Committee at Western University (protocol 2014\u2013016) and are in compliance with Canadian and National Institute of Health Guides for the Care and Use of Laboratory Animals (NIH Publication #80\u201323).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"First author holds copyright to data and figures reproduced from dissertation submitted to the University of Western Ontario.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}