| dc.description.abstract | Dementia is a decline in cognitive abilities that impairs an individual’s ability
to engage in everyday activities, commonly caused by Alzheimer’s disease
(60-70% of cases). Current biomarkers are usually derived using
neuroimaging or from cerebrospinal fluid (CSF) and include a decrease in
amyloid beta 42 fragment (Aß42) and an increase in phosphorylated tau (p-
tau). Blood-based biomarkers are an attractive alternative due to lower
invasiveness and cost, yet accurate interpretation remains a significant
challenge in reflecting AD pathology. This review aims to assess the plasma
proteomic changes in AD and dementia by examining the replicability of
blood plasma biomarkers and identifying shared pathways and distinctive
AD-specific markers. After excluding 307 records from a total of 316,
fourteen articles were included in the literature review, reporting 33
association studies with 7931, 8687, and 145 AD, dementia, and Mild
Cognitive Impairment (MCI) subjects, respectively. We identified 1579
unique proteins associated with the conditions, with the majority (80.7%)
originating from AD vs control studies.To ensure reliable results for
subsequent analyses, we applied replicability filters based on the number of
proteins that met the threshold. In the overlap of 215 proteins between AD
and dementia, enriched biological functions implicated blood coagulation,
hemostasis, cell secretion, organization, and adhesion. Specific genes, such
as SERPINF2, associated with the plasmin cascade and
neurodegeneration, emerged as potential indicators of AD-related vascular
changes. AD-specific proteins revealed enriched biological functions related
to magnesium ion response, neuromuscular junction development, and
postsynapse organization. APP and LRRK2, associated with early onset AD
and dementia, were replicated in our review. Comparisons with a recent
proteomics study using brain cortex tissue underscored the need for a multi-
tissue approach in biomarker discovery for AD. While overlaps in some
genes (e.g., APP, GFAP) suggested shared molecular mechanisms across
tissues, distinctive sets of genes indicated tissue-specific responses to AD.
Despite challenges in consistency and heterogeneity, the findings encourage
further exploration of blood-based biomarkers. Recognizing the complexity in
identifying these markers and their interplay with central nervous system
processes is crucial for advancing our understanding of the mechanisms
associated with AD and dementia. | |
