Aβ40 Fibril Assembly on Human Cerebral Smooth Muscle Cells Impairs Cell Viability.

Cerebral vascular deposition of the amyloid-β (Aβ) peptide, a condition known as cerebral amyloid angiopathy (CAA), is associated with intracerebral hemorrhaging and contributes to disease progression in Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID). Familial mutations at positions 22 and 23 within the Aβ peptide lead to early onset and severe CAA pathology. Here, we evaluate the effects of fibrillar Aβ peptides on the viability of primary-cultured human cerebral smooth muscle (HCSM) cells, which are the major site of amyloid deposition in cerebral blood vessel walls.

Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer's disease.

Brain waste clearance from the interstitial fluid environment is challenging to measure, which has contributed to controversy regarding the significance of glymphatic transport impairment for neurodegenerative processes. Dynamic contrast enhanced MRI (DCE-MRI) with cerebrospinal fluid administration of Gd-tagged tracers is often used to assess glymphatic system function. We previously quantified glymphatic transport from DCE-MRI data utilizing regularized optimal mass transport (rOMT) analysis, however, information specific to glymphatic clearance was not directly derived.

Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.

Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid β-protein (Aβ) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aβ promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology.

Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies.

The brain's network of perivascular channels for clearance of excess fluids and waste plays a critical role in the pathogenesis of several neurodegenerative diseases including cerebral amyloid angiopathy (CAA). CAA is the main cause of hemorrhagic stroke in the elderly, the most common vascular comorbidity in Alzheimer's disease and also implicated in adverse events related to anti-amyloid immunotherapy. Remarkably, the mechanisms governing perivascular clearance of soluble amyloid β-a key culprit in CAA-from the brain to draining lymphatics and systemic circulation remains poorly understood.