Critical threshold cerebral hypoperfusion causes Alzheimer's disease?

Area of Science:

• Neuroscience
• Pathology
• Gerontology

Background:

• The exact cause of Alzheimer's disease (AD) remains elusive despite extensive research.
• Key pathological events in AD development require a unifying hypothetical explanation.

Purpose of the Study:

• To present a hypothetical model for Alzheimer's disease pathogenesis.
• To explain the interplay of aging and reduced cerebral perfusion in AD development.
• To discuss potential therapeutic targets based on the proposed pathogenesis.

Main Methods:

• Review of basic and clinical evidence.
• Hypothetical assembly of pathological events.
• Analysis of contributing factors to cerebral hypoperfusion.

Main Results:

• Impaired cerebral perfusion, originating in microvasculature, disrupts glucose and oxygen delivery.
• Breakdown of metabolic energy pathways in brain cells is linked to hypoperfusion.
• Critical threshold cerebral hypoperfusion, driven by aging and other conditions, initiates neurodegeneration.

Conclusions:

• Advanced aging combined with conditions lowering cerebral perfusion are necessary for AD onset.
• Critical threshold cerebral hypoperfusion is a self-perpetuating process leading to neuronal destabilization.
• This hypoperfusion model explains AD hallmarks like plaques, tangles, and amyloid angiopathy.