Amyloid pathology and synaptic loss in pathological aging.
Aged
Aged, 80 and over
Aging
/ pathology
Alzheimer Disease
/ pathology
Amyloid beta-Peptides
/ analysis
Autopsy
Cerebellum
/ chemistry
Female
Frontal Lobe
/ chemistry
Humans
Male
Mass Spectrometry
Middle Aged
Nerve Tissue Proteins
/ chemistry
Occipital Lobe
/ chemistry
Plaque, Amyloid
/ pathology
Synapses
/ chemistry
Alzheimer's disease
RBM3
SNAP-25
amyloid beta
immunoprecipitation
mass spectrometry
pathological aging
synaptophysin
synaptotagmin-1
synaptotagmin-7
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
24
07
2021
received:
30
10
2020
accepted:
26
07
2021
pubmed:
3
9
2021
medline:
20
11
2021
entrez:
2
9
2021
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory dysfunction and cognitive decline. Pathological aging (PA) describes patients who are amyloid-positive but cognitively unimpaired at time of death. Both AD and PA contain amyloid plaques dominated by amyloid β (Aβ) peptides. In this study, we investigated and compared synaptic protein levels, amyloid plaque load, and Aβ peptide patterns between AD and PA. Two cohorts of post-mortem brain tissue were investigated. In the first, consisting of controls, PA, AD, and familial AD (FAD) individuals, synaptic proteins extracted with tris(hydroxymethyl)aminomethane-buffered saline (TBS) were analyzed. In the second, consisting of tissue from AD and PA patients from three different regions (occipital lobe, frontal lobe, and cerebellum), a two-step extraction was performed. Five synaptic proteins were extracted using TBS, and from the remaining portion Aβ peptides were extracted using formic acid. Subsequently, immunoprecipitation with several antibodies targeting different proteins/peptides was performed for both fractions, which were subsequently analyzed by mass spectrometry. The levels of synaptic proteins were lower in AD (and FAD) compared with PA (and controls), confirming synaptic loss in AD patients. The amyloid plaque load was increased in AD compared with PA, and the relative amount of Aβ40 was higher in AD while for Aβ42 it was higher in PA. In AD loss of synaptic function was associated with increased plaque load and increased amounts of Aβ40 compared with PA cases, suggesting that synaptic function is preserved in PA cases even in the presence of Aβ.
Substances chimiques
Amyloid beta-Peptides
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
258-272Informations de copyright
© 2021 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
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