Monitoring synaptic pathology in Alzheimer's disease through fluid and PET imaging biomarkers: a comprehensive review and future perspectives.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
16 Jan 2024
16 Jan 2024
Historique:
received:
06
07
2023
accepted:
12
12
2023
revised:
04
12
2023
medline:
17
1
2024
pubmed:
17
1
2024
entrez:
16
1
2024
Statut:
aheadofprint
Résumé
Alzheimer's disease (AD) is currently constrained by limited clinical treatment options. The initial pathophysiological event, which can be traced back to decades before the clinical symptoms become apparent, involves the excessive accumulation of amyloid-beta (Aβ), a peptide comprised of 40-42 amino acids, in extraneuronal plaques within the brain. Biochemical and histological studies have shown that overaccumulation of Aβ instigates an aberrant escalation in the phosphorylation and secretion of tau, a microtubule-binding axonal protein. The accumulation of hyperphosphorylated tau into intraneuronal neurofibrillary tangles is in turn correlated with microglial dysfunction and reactive astrocytosis, culminating in synaptic dysfunction and neurodegeneration. As neurodegeneration progresses, it gives rise to mild clinical symptoms of AD, which may eventually evolve into overt dementia. Synaptic loss in AD may develop even before tau alteration and in response to possible elevations in soluble oligomeric forms of Aβ associated with early AD. These findings largely rely on post-mortem autopsy examinations, which typically involve a limited number of patients. Over the past decade, a range of fluid biomarkers such as neurogranin, α-synuclein, visinin-like protein 1 (VILIP-1), neuronal pentraxin 2, and β-synuclein, along with positron emission tomography (PET) markers like synaptic vesicle glycoprotein 2A, have been developed. These advancements have facilitated the exploration of how synaptic markers in AD patients correlate with cognitive impairment. However, fluid biomarkers indicating synaptic loss have only been validated in cerebrospinal fluid (CSF), not in plasma, with the exception of VILIP-1. The most promising PET radiotracer, [
Identifiants
pubmed: 38228892
doi: 10.1038/s41380-023-02376-6
pii: 10.1038/s41380-023-02376-6
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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