Zwergal A, la Fougere C, Lorenzl S, et al: Postural imbalance and falls in PSP correlate with functional pathology of the thalamus. Neurology 77:101, 2011.
Figure 38-1. Photomicrograph of Alzheimer amyloid plaques and neurofibrillary tangles. Bielschowsky silver stain.
NH2COOH*****Mutations in APP,    or ˜ secretase,and the Apo E4 allele enhance toxicity. ß secretaseAPP˜ secretaseAPPsßß stubApo EAß42FibrillogenesisAmyloidneurotoxicityDownsyndromeß ˛ß˜
Figure 38-2. Diagram of proteolysis of amyloid precursor protein (APP). When APP is cleaved sequentially by β secretase and then secretase, the resulting amyloid protein can be 40 (Aβ40) or 42 (Aβ42) amino acids in length. The latter favors the formation of aggregated fibrillary amyloid protein (fibrillogenesis) rather than normal APP degradation. The fibrillary form of amyloid is neurotoxic, a mechanism favored as the cause of cell damage in Alzheimer disease. Formation of Aβ42 is promoted by mutations, either in the APP gene itself or in the presenilins. In Down syndrome, excess production of APP and its product Aβ42 is caused by triplication of the long arm of chromosome 21, the location of the APP gene. The Apo E4 allele is associated with inadequate clearance of Aβ42 and is another mechanism that promotes fibrillogenesis. (Modified by permission from Sisodia SS, St. George–Hyslop PH: γ-Secretase, notch, Aβ and Alzheimer disease: Where do the presenilins fit in? Nat Rev Neurosci 3:281–290, 2002.)
Figure 38-3. Top: Coronal T1-weighted MRI of a 74-year-old man with moderate Alzheimer-type dementia. Diffuse cerebral and hippocampal atrophy with ex vacuo ventricular and cortical sulcal dilation is noted. Bottom: Coronal T1-weighted MRI of a 70-year-old woman with behavioral variant frontotemporal lobar dementia. Atrophy of the right greater than left temporal lobes is out of proportion to atrophy of the frontal and parietal lobes.
Figure 38-4. Axial CT from a 54-year-old mildly demented woman with a 10-year history of Huntington chorea. The bulge in the inferolateral border of the lateral ventricle, normally created by the head of the caudate nucleus, is absent. There is also diffuse enlargement of the lateral ventricles.
Figure 38-5. Photomicrograph of a round Lewy body inclusion in the cytoplasm of a nigral neuron. (Hematoxylin and eosin [H&E] staining.) (From Frosch MP, et al: The central nervous system. In Robbins SL, et al (eds): Robbins and Cotran Pathologic Basis of Disease, 8th ed. Philadelphia, Saunders/Elsevier, 2010.)