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Cited by 42Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Postsynaptic Proteome of Non-Demented Individuals with Alzheimer’s Disease Neuropathology

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Zolochevska, Olga, Bjorklund, Nicole, Woltjer, Randall, Wiktorowicz, John E., Taglialatela, Giulio·2018·Journal of Alzheimer’s Disease
DOI 10.3233/jad-180179PMC PMC6130411
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Abstract

Some individuals, here referred to as Non-Demented with Alzheimer’s Neuropathology (NDAN), retain their cognitive function despite the presence of amyloid plaques and tau tangles typical of symptomatic Alzheimer’s disease (AD). In NDAN, unlike AD, toxic amyloid-β oligomers do not localize to the postsynaptic densities (PSDs). Synaptic resistance to amyloid-β in NDAN may thus enable these individuals to remain cognitively intact despite the AD-like pathology. The mechanism(s) responsible for this resistance remains unresolved and understanding such protective biological processes could reveal novel targets for the development of effective treatments for AD. The present study uses a proteomic approach to compare the hippocampal postsynaptic densities of NDAN, AD, and healthy age-matched persons to identify protein signatures characteristic for these groups. Subcellular fractionation followed by 2D gel electrophoresis and mass spectrometry were used to analyze the PSDs. We describe fifteen proteins which comprise the unique proteomic signature of NDAN PSDs, thus setting them apart from control subjects and AD patients.

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  • Many older individuals have considerable Aβ in the brain, yet do not display cognitive deficits or dementia when compared to age-matched controls without Aβ accumulation.

    “Many older individuals have considerable Aβ in the brain, yet do not display cognitive deficits or dementia when compared to age-matched controls without Aβ accumulation [107,108].”

    From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [108]

    The Introduction describes individuals with Alzheimer’s-like pathology who experience no cognitive decline, and Methods > Case subjects says both NDAN subjects and controls had normal cognitive and functional examinations. The Results identify the controls as age-matched. Our copy does not establish that those controls had no Aβ accumulation, and it says “some” individuals rather than quantifying them as “many” (page numbers unavailable). (LLM, conf=0.82)

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Authors
Zolochevska, O., Bjorklund, N., Woltjer, R., Wiktorowicz, J. E., & Taglialatela, G.
Affiliations
  • The University of Texas Medical Branch at Galveston (US)
  • Oregon Health & Science University (US)
Corresponding author
Taglialatela, Giulio
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2018-07-30
Volume
65
Issue
2
Pages
659-682
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-180179
PMC
PMC6130411
OpenAlex
W2887785247
Cited by
42
References
167
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 7
FWCI
3.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (R01AG042890, F31AG057217)
  • National Institute of Environmental Health Sciences (T32ES007254)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Female, Hippocampus, Humans, Male, Mass Spectrometry, Subcellular Fractions, Electrophoresis, Gel, Two-Dimensional, Proteome, Proteomics, Post-Synaptic Density

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