Iowa Variant of Familial Alzheimer’s Disease

摘要: Mutations within the amyloid-β (Aβ) sequence, especially those clustered at residues 21-23, which are linked to early onset familial Alzheimer’s disease (AD), primarily associated with cerebral amyloid angiopathy (CAA). The basis for this predominant vascular burden and differential clinical phenotypes of hemorrhage/stroke in some patients dementia others remain unknown. AβD23N Iowa mutation is progressive AD-like dementia, often without clinically manifested intracerebral hemorrhage. Neuropathologically, characterized by preamyloid deposits, severe CAA, abundant neurofibrillary tangles presence remarkably few mature plaques. Biochemical analyses using a combination immunoprecipitation, mass spectrometry, amino acid Western blot analysis performed after sequential tissue extractions separately isolate soluble components, preamyloid, fibrillar species indicated that deposits complex mixtures mutated nonmutated Aβ molecules. These molecules exhibited various degrees solubility, were highly heterogeneous both N- C-termini, showed partial aspartate isomerization positions 1, 7, 23. This collection species—the brain peptidome—contained clear imprints clearance mechanisms yet highlighted unique neuropathological features shared non-Aβ amyloidosis, Danish coexist extensive pre-amyloid deposition virtual absence lesions. data therefore challenge importance neuritic plaques as sole contributors development dementia.