A cortical form of CADASIL with cerebral Aβ amyloidosis

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was diagnosed by genetic testing in a 53-year-old patient, 10 years before death. Following two strokes with partial recovery, he developed rapidly progressive cognitive decline 3 years before death. Neuropathology confirmed CADASIL. Characteristic arteriolar changes were associated with subcortical infarcts, and status cribrosus in basal ganglia and the cortico-subcortical junctions. Leukoencephalopathy was very mild. Severe arteriolar changes in the cerebral cortex and leptomeninges were associated with numerous intracortical microinfarcts. There was abundant Abeta deposition throughout the cerebral cortex, mainly as A beta 42 diffuse plaques, frequently periarteriolar. There was no cerebral amyloid angiopathy apart from rare A beta 40 deposits around Notch3-positive deposits. Amyloid plaques were rare. Tau pathology was minimal. Alzheimer disease associated with CADASIL has been described, but the few reported cases had abundant amyloid plaques, amyloid angiopathy, fibrillar plaques and neurofibrillary tangles. A beta accumulation could result from abnormal A beta synthesis or impaired elimination due to the arteriolar changes of CADASIL. We did not find A beta deposits in our other CADASIL cases with milder cortical arteriolar changes. Additional genetic predisposing factors were not identified. This case suggests that besides the classical, purely subcortical form of CADASIL, a cortical form with numerous lacunar infarcts and A beta deposition in the cerebral cortex may occur and may be difficult to differentiate clinically from Alzheimer disease.