Rare Diseases Symptoms Automatic Extraction

Alzheimer's disease and CADASIL are heritable, adult-onset dementias that both involve damaged small blood vessels.

[cadasil]

This essay explores an alternative pathway to Alzheimer's dementia that focuses on damage to small blood vessels rather than late-stage toxic amyloid deposits as the primary pathogenic mechanism that leads to irreversible dementia. While the end-stage pathology of AD is well known, the pathogenic processes that lead to disease are often assumed to be due to toxic amyloid peptides that act on neurons, leading to neuronal dysfunction and eventually neuronal cell death. Speculations as to what initiates the pathogenic cascade have included toxic abeta peptide aggregates, oxidative damage, and inflammation, but none explain why neurons die. Recent high-resolution NMR studies of living patients show that lesions in white matter regions of the brain precede the appearance of amyloid deposits and are correlated with damaged small blood vessels. To appreciate the pathogenic potential of damaged small blood vessels in the brain, it is useful to consider the clinical course and the pathogenesis of CADASIL, a heritable arteriopathy that leads to damaged small blood vessels and irreversible dementia. CADASIL is strikingly similar to early onset AD in that it is caused by germ line mutations in NOTCH 3 that generate toxic protein aggregates similar to those attributed to mutant forms of the amyloid precursor protein and presenilin genes. Since NOTCH 3 mutants clearly damage small blood vessels of white matter regions of the brain that lead to dementia, we speculate that both forms of dementia may have a similar pathogenesis, which is to cause ischemic damage by blocking blood flow or by impeding the removal of toxic protein aggregates by retrograde vascular clearance mechanisms.

Diseases presenting "damaged small blood vessels in the brain" symptom

  • cadasil

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