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• W2046240344 abstract "Clinico-pathological studies have repeatedly shown a strong relationship between the density of cortical neuritic plaques (NP) and neurofibrillary tangles (NFT) with dementia severity. However, accumulating recent evidence from multiple laboratories suggests that these relationships are measurably less strong in the brains of oldest-old (OO, > 85 years) people with dementia relative to young-old (YO) persons. We tested the hypothesis that oligomeric Ab (oAb) was associated with dementia irrespective of the deposition of insoluble Ab and the formation of NPs. Postmortem specimens from the superior temporal gyrus (Bm22) of 111 cases ranging in age between 70-102 years with no neuropathology, or only AD-associated neuropathology was studied. Subjects with CDR scores of 0 and 0.5 were designated as non-demented and those with CDR scores > 1 as demented. For Aßx-40 and Aßx-42 ELISAs, antibodies 2G3 and 21F12 were used for capture and 6E10 for detection. For oAb, the 3D6-3D6 capture and detection protocols was used (Arch Neurol 2009;66:190-9). As expected, dementia was associated with higher number of NPs (p < 0.0001) and ELISA measures of soluble and insoluble Ab40 and Ab42, but the dementia-associated rise in these measures diminished to non-significant by age 90 and beyond. In contrast, the levels of oAb were significantly elevated in the dementia groups (p < 0.0001) and remained so (p < 0.05) at virtually all ages. In YO persons all forms of Ab were robustly correlated with the degree of dementia (p < 0.006), in OO persons only the levels of oAb correlated significantly with CDR (r = 0.46, p < 0.05). Increased levels of brain oAb are central to dementia, even in OO persons when the ability of NPs and levels of soluble and insoluble Ab-40 and Ab-42 to distinguish dementia from non-dementia has become tenuous. These results support the involvement of Ab in dementia and AD pathogenesis, but suggest that in contrast to fibrillar Ab deposits in NPs, increased levels of oAb may be wholly or partially responsible for dementia in both YO and OO persons. oAb is a potentially important target for therapeutic intervention not only in the rapidly expanding population of the OO, but for persons with AD dementia at any age." @default.
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• W2046240344 date "2011-07-01" @default.
• W2046240344 modified "2023-10-18" @default.
• W2046240344 title "P2-283: Oligomeric abeta associated with dementia in young-old and oldest-old persons" @default.
• W2046240344 doi "https://doi.org/10.1016/j.jalz.2011.05.1161" @default.
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