Meta-analysis of synaptic pathology in Alzheimer's disease reveals selective molecular vesicular machinery...

Area of Science:

• Neuroscience
• Pathology
• Biochemistry

Background:

• Synaptic loss correlates with cognitive deficits in Alzheimer's disease (AD).
• Oligomeric amyloid-β species are implicated in synaptic pathology.
• Previous studies on AD synaptic pathology often had limited sample sizes.

Purpose of the Study:

• To conduct a systematic meta-analysis of studies investigating synaptic and synaptic marker loss in Alzheimer's disease.
• To establish the extent and timing of synaptic loss in AD pathogenesis.
• To determine if presynaptic or postsynaptic markers are more affected in AD.

Main Methods:

• A meta-analysis was performed on 417 publications reporting postmortem synapse and synaptic marker loss in AD patients.
• Two separate meta-analyses were conducted using a unified database.
• Standard mean differences were calculated to quantify the effects.

Main Results:

• Meta-analysis confirmed that synaptic loss is an early event in AD pathogenesis across selected brain regions.
• A second meta-analysis of 57 synaptic markers revealed a greater impact on presynaptic markers compared to postsynaptic markers.
• Consistent synaptic loss was observed across brain regions.

Conclusions:

• Synaptic loss is a consistent feature across brain regions in Alzheimer's disease.
• Molecular machinery, including endosomal pathways, vesicular assembly, glutamate receptors, and axonal transport, is frequently affected in AD.
• Presynaptic markers are more vulnerable than postsynaptic markers in AD synaptic pathology.