Synaptic biomarkers in Alzheimer's disease dementia and mild cognitive impairment: A systematic review and meta‐analysis

INTRODUCTION: Alzheimer's disease (AD) is characterized by synaptopathy, a neuropathological feature that can contribute to underlying cognitive decline. Here, we evaluate potential cerebrospinal fluid (CSF) and blood-based synaptic biomarkers in AD dementia and its earliest clinical stage, mild cognitive impairment (MCI). METHODS: Articles that measured a subset of CSF and/or blood-based synaptic biomarkers in AD dementia, MCI, and/or healthy controls were included. A random-effects model was used to determine standardized mean differences and 95% confidence intervals. RESULTS: In total, 65 study cohorts were included for meta-analysis and 12 for qualitative review. Several CSF (synaptosomal-associated protein 25 [SNAP-25], growth-associated protein 43 [GAP-43], neuronal pentraxin receptor, neuronal pentraxin-1, neuronal pentraxin-2, synaptotagmin-1, syntaxin-1B, and vesicle-associated membrane protein 2) and blood-based (SNAP-25, GAP-43, and synaptotagmin-1) synaptic biomarkers were altered in AD dementia and/or MCI. DISCUSSION: Further evaluation of these identified biomarkers may enrich our understanding of AD pathophysiology and disease trajectory, as well as inform future treatment interventions.