Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis

Abstract

Insurmountable evidence has demonstrated a strong association between Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA), along with various other cerebrovascular diseases. One form of CAA, which is the accumulation of amyloid-beta peptides (Aβ) along cerebral vessel walls, impairs perivascular drainage pathways and contributes to cerebrovascular dysfunction in AD. To date, CAA research has been primarily focused on arterial Aβ, while the accumulation of Aβ in veins and venules were to a lesser extent. In this review, we describe preclinical models and clinical studies supporting the presence of venular amyloid and potential downstream pathological mechanisms that affect the cerebrovasculature in AD. Venous collagenosis, impaired cerebrovascular pulsatility, and enlarged perivascular spaces are exacerbated by venular amyloid and increase Aβ deposition, potentially through impaired perivascular clearance. Gaining a comprehensive understanding of the mechanisms involved in venular Aβ deposition and associated pathologies will give insight to how CAA contributes to AD and its association with AD-related cerebrovascular disease. Lastly, we suggest that special consideration should be made to develop Aβ-targeted therapeutics that remove vascular amyloid and address cerebrovascular dysfunction in AD.

Cerebrovascular phenotypes in mouse models of Alzheimer’s disease

“…However, cerebrovascular decrements have focused primarily on changes in arteries and capillaries and attention to venule pathology has been largely overlooked. Indeed, venular amyloid have significant consequences on AD pathology 148 and evaluation of both arteriole and venule aberrations should be seriously considered in future studies.…”

The aging venous system: from varicosities to vascular cognitive impairment

“…Research into the pathogenesis of cerebral amyloid angiopathy has been primarily focused on Aβ deposition in the wall of arterial vessels. Yet, there is also increasing evidence from preclinical studies and clinical investigations that veins and venules are also affected by accumulation of Aβ likely through impaired perivascular clearance [ 202 , 203 ]. It has been proposed that venular amyloidosis exacerbates microvascular pathologies associated with AD and may promote the development of amyloid plaques in the brain parenchyma as well [ 203 ].…”

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

“…248,253 Typical features of Parkinson's disease are the ubiquitous presence of alpha-synuclein-positive Lewy bodies, loss of dopamine neurons, and dystrophic Lewy neurites. 248,254,255 RAAS also plays an irreplaceable role in brain function, and studies have shown that renin, ACE, Ang II, and Ang (1-7) are found in the central nervous system. They are involved in the regulation of blood pressure, water and food intake, maintenance of the bloodbrain barrier, and even in movement, learning, memory, and emotional control.…”