II. Diseases primarily affecting the cerebral cortex
A. Alzheimer Disease (AD) - deposits of both tau (neurofibrillary tangles) and amyloid (neuritic plaques)
1. Age of Onset: Usually after 40 years; incidence increases with increasing age.
2. Incidence: Occasionally familial (about 10% of cases), some with autosomal dominant inheritance pattern; usually sporadic; affects 10% of persons over 65; nearly 50% of those over 85. Pathological changes identical to those observed in AD occur in almost all patients with trisomy 21 (Down's syndrome) who survive beyond 45 years. The incidence is increased in individuals homozygous for the apoE4 allele. There are autosomal dominant familial forms (rare) with a mutation in the presenilin 1 or presenilin 2 gene (genetic testing is available).
3. Location of Lesions: cortex; hippocampus; basal forebrain, especially basal nucleus of Meynert (which contains cholinergic neurons projecting to cortex); and other regions.