{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:49:40Z","timestamp":1783723780993,"version":"3.55.0"},"reference-count":58,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,3,7]]},"abstract":"<jats:p>Background: Phosphorylated cytoplasmic tau inclusions correlate with and precede cognitive deficits in Alzheimer\u2019s disease (AD). However, pathological tau accumulation and relationships to synaptic changes remain unclear. Objective: To address this, we examined postmortem brain from 50 individuals with the full spectrum of AD (clinically and neuropathologically). Total tau, pTau231, and AMPA GluR1 were compared across two brain regions (entorhinal and middle frontal cortices), as well as clinically stratified groups (control, amnestic mild cognitive impairment, AD dementia), NIA-AA Alzheimer\u2019s Disease Neuropathologic Change designations (Not, Low, Intermediate, High), and Braak tangle stages (1\u20136). Significant co-existing pathology was excluded to isolate changes attributed to pathologic AD. Methods: Synaptosomal fractionation and staining were performed to measure changes in total Tau, pTau231, and AMPA GluR1. Total Tau and pTau231 were quantified in synaptosomal fractions using Quanterix Simoa HD-X. Results: Increasing pTau231 in frontal postsynaptic fractions correlated positively with increasing clinical and neuropathological AD severity. Frontal cortex is representative of early AD, as it does not become involved by tau tangles until late in AD. Entorhinal total tau was significantly higher in the amnestic mild cognitive impairment group when compared to AD, but only after accounting for AD associated synaptic changes. Alterations in AMPA GluR1 observed in the entorhinal cortex, but not middle frontal cortex, suggest that pTau231 mislocalization and aggregation in postsynaptic structures may impair glutamatergic signaling by promoting AMPA receptor dephosphorylation and internalization. Conclusion: Results highlight the potential effectiveness of early pharmacological interventions targeting pTau231 accumulation at the postsynaptic density.<\/jats:p>","DOI":"10.3233\/jad-220848","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T11:56:42Z","timestamp":1675166202000},"page":"241-260","source":"Crossref","is-referenced-by-count":15,"title":["Accumulation of pTau231 at the Postsynaptic Density in Early Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"92","author":[{"given":"Jaclyn","family":"Lilek","sequence":"first","affiliation":[{"name":"Department of Pathology, Northwestern University, Illinois, USA"},{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaouther","family":"Ajroud","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Illinois, USA"},{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Z.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sesha","family":"Krishnamachari","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Minnesota, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"Ghourchian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Gefen","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"},{"name":"Department of Psychiatry and Behavioral Sciences, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callen L.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allegra","family":"Kawles","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwen","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Northwestern University, Illinois, USA"},{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica F.","family":"Tranovich","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford R.","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M-Marsel","family":"Mesulam","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"},{"name":"Department of Neurology, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Ross","family":"Reichard","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University, Illinois, USA"},{"name":"Division of Biostatistics, Department of Preventative Medicine, Feinberg School of Medicine, Northwestern University, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Knopman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Minnesota, Minnesota, USA"},{"name":"N. 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A component of Alzheimer paired helical filaments","volume":"261","author":"Grundke-Iqbal","year":"1986","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-220848_ref4","doi-asserted-by":"crossref","first-page":"7501","DOI":"10.1073\/pnas.1504081112","article-title":"Tau stabilizes microtubules by binding at the interface between tubulin heterodimers","volume":"112","author":"Kadavath","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-220848_ref5","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1016\/j.cell.2021.03.032","article-title":"Reducing acetylated tau is neuroprotective in brain injury","volume":"184","author":"Shin","year":"2021","journal-title":"Cell"},{"key":"10.3233\/JAD-220848_ref6","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.cell.2020.10.029","article-title":"Tau PTM profiles identify patient heterogeneity and stages of Alzheimer\u2019s 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regions based on a combined analysis of cyto- and chemoarchitecture","volume":"523","author":"Ding","year":"2015","journal-title":"J Comp Neurol"},{"key":"10.3233\/JAD-220848_ref34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40478-022-01324-9","article-title":"Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling","volume":"10","author":"Walker","year":"2022","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-220848_ref35","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41587-020-0472-9","article-title":"Multiplex digital spatial profiling of proteins and RNA in fixed tissue","volume":"38","author":"Merritt","year":"2020","journal-title":"Nat Biotechnol"},{"key":"10.3233\/JAD-220848_ref36","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/path.5223","article-title":"New tools for pathology: A User\u2019s review of a highly multiplexed method for in situ analysis 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