Can disturbed brain microcirculation cause Alzheimer's disease?

Area of Science:

• Neuroscience
• Pathology
• Biomedical Engineering

Background:

• Alzheimer's disease (AD) is characterized by neurodegeneration and cognitive decline.
• Ultrastructural studies reveal significant angio-architectural distortions in cerebral capillaries of AD patients.
• Reduced cerebral blood flow (CBF), glucose metabolism, and oxygen utilization correlate with AD severity.

Purpose of the Study:

• To propose a hypothetical model for Alzheimer's disease pathogenesis and progression.
• To elucidate the role of cerebral microvascular dysfunction in AD.
• To link capillary degeneration to neuronal damage and hallmark AD pathologies.

Main Methods:

• Review and synthesis of ultrastructural studies on cerebral capillaries in AD.
• Development of a hypothetical model integrating vascular, haemorheological, and neuropathological factors.
• Analysis of the interplay between aging, amyloid deposits, and microvascular integrity.

Main Results:

• Ageing and AD-related factors (amyloid, basement membrane thickening) cause progressive capillary degeneration.
• Microvascular damage leads to haemorheological compromise, including increased resistance and altered blood flow.
• Impaired nutrient and oxygen delivery to neurons results in ischemic stress and reactive astrocytosis.

Conclusions:

• Cerebral capillary degeneration is a critical factor in Alzheimer's disease pathogenesis.
• Disturbed blood flow and impaired nutrient delivery contribute to neuronal dysfunction and death.
• Reactive glia, potentially expressing amyloid precursor protein, play a role in plaque and tangle formation, driving disease progression.