Presynaptic failure in Alzheimer's disease.

Area of Science:

• Neuroscience
• Molecular Biology
• Pathology

Background:

• Synaptic loss correlates with cognitive deficits in Alzheimer's disease (AD).
• Early AD stages show synaptic alterations before widespread neurodegeneration.
• Most AD research focuses on postsynaptic changes, neglecting presynaptic mechanisms.

Purpose of the Study:

• To review literature on the presynaptic component of AD synaptic pathology.
• To highlight the presynaptic physiological functions of major AD-related proteins.
• To discuss how presynaptic dysfunction contributes to AD hallmarks.

Main Methods:

• Literature review of studies on Alzheimer's disease mouse models and human brains.
• Analysis of the roles of amyloid precursor protein (APP), presenilins (PS1/PS2), and tau in presynaptic physiology.
• Examination of mechanisms including receptor binding, calcium homeostasis, and vesicle regulation.

Main Results:

• AD pathology includes a significant presynaptic component.
• APP, presenilins, and tau have critical presynaptic functions.
• Impairment of these presynaptic functions by AD-related proteins contributes to synaptic dysfunction and cognitive deficits.

Conclusions:

• Presynaptic failure is a key pathological mechanism in Alzheimer's disease.
• Understanding presynaptic roles of APP, presenilins, and tau is crucial for AD research.
• Targeting presynaptic mechanisms may offer new therapeutic strategies for AD.