Abstract
Handb Clin Neurol. 2024;204:289-315. doi: 10.1016/B978-0-323-99209-1.00010-7.
ABSTRACT
Familial cerebral amyloid disorders are characterized by the accumulation of fibrillar protein aggregates, which deposit in the parenchyma as plaques and in the vasculature as cerebral amyloid angiopathy (CAA). Amyloid β (Aβ) is the most common of these amyloid proteins, accumulating in familial and sporadic forms of Alzheimer's disease and CAA. However, there are also a number of rare, hereditary, non-Aβ cerebral amyloidosis. The clinical manifestations of these familial cerebral amyloid disorders are diverse, including cognitive or neuropsychiatric presentations, intracerebral hemorrhage, seizures, myoclonus, headache, ataxia, and spasticity. Some mutations are associated with extensive white matter hyperintensities on imaging, which may or may not be accompanied by hemorrhagic imaging markers of CAA; others are associated with occipital calcification. We describe the clinical, imaging, and pathologic features of these disorders and discuss putative disease mechanisms. Familial disorders of cerebral amyloid accumulation offer unique insights into the contributions of vascular and parenchymal amyloid to pathogenesis and the pathways underlying white matter involvement in neurodegeneration. With Aβ immunotherapies now entering the clinical realm, gaining a deeper understanding of these processes and the relationships between genotype and phenotype has never been more relevant.
PMID:39322385 | DOI:10.1016/B978-0-323-99209-1.00010-7