ANTIGENIC PROFILE OF PLAQUES AND NEUROFIBRILLARY TANGLES IN THE AMYGDALA IN DOWNS-SYNDROME - A COMPARISON WITH ALZHEIMERS-DISEASE

Most patients with Down's syndrome (DS) undergo a premature cognitive decline with aging, and eventually develop the neuropathologic changes of Alzheimer's disease (AD), including amyloid-containing neuritic plaques, and the formation of neurofibrillary tangles. The amygdala is a focus of marked neuropathologic change in older patients with DS and in AD. We examined the amygdala with immunocytochemical and histochemical methods in 6 cases with DS, ages 19, 20, 27, 29, 56 and 64 years and compared them to 4 cases with AD, ages 54, 76, 77 and 80 years. An antiserum to the A4 amyloid peptide demonstrated amyloid deposition in plaques in all 10 cases. Plaques were also revealed in all cases by the Alcian blue stain for glycosaminoglycans and by the Bielschowsky and Bodian silver stains. An antiserum to alpha-1-antichymotrypsin (ACT) showed plaques in the AD cases and in the 19, 56, and 64 year old DS cases. Neurofibrillary tangles were observed with silver stains only in the older DS and in the AD cases, and not in the 19, 20, 27 and 29 year old DS cases. Likewise, antisera to paired helical filament, to microtubule associated proteins tau and microtubule associated protein-2 (MAP-2), and to ubiquitin, all of which are components of neurofibrillary tangles, reacted with tangles and abnormal neurites only in the older DS and the AD cases. An antiserum to neurofilament epitopes labeled NFTs in the older DS cases and the AD cases, but not in the younger DS cases, except for two intraneuronal NFTs in the 27 year old case. Extensive gliosis was revealed by glial fibrillary acidic protein and S-100 antisera in the older DS and the AD cases. Our findings suggest that in the amygdala in DS and possibly AD, amyloid and glycosaminoglycan deposition in plaques may precede abnormal protein expression in neurofibrillary tangles. ACT deposition may also appear early in some cases. Anatomically, amyloid, glycosaminoglycan, and ACT deposition, and neurofibrillary tangle formation were greatest in the cortical and basal regions of the amygdala.