Neuropathological Changes in Down's Syndrome Hippocampal Formation

Presence of the Apolipoprotein E Type ε4 Allele Is Not Associated with Neurofibrillary Pathology or Biochemical Changes to Tau Protein

“…Our findings on the quan titative differences in the amyloid burden as a function of the APOE genotype are in agreement with findings from several studies, demonstrating an increase in amyloid load not only in e4 allele carriers with a diagnosis of AD [24][25][26][27]36], but also in Down's syndrome cases [43], Lewy body disease [44], cerebral amyloid angiopathy [18], Parkinson's disease [17] and head injury [45], Other studies, however, have not shown that amyloid burden is necessarily influenced by APOE genotype [46][47][48]. It seems likely, therefore, that the APOE e4 allele influences the probability of initiation of processes leading to amy loid deposits and that the mechanism affecting amyloid processing may be the same in a variety of neurodegenerative disorders, rather than being specific for AD.…”

Chapter 4 Alzheimer's Disease in Adults with Down Syndrome

“…In numerous studies, participants with Alzheimer's disease have been found to have higher frequencies of the APOE ε4 allele compared with those without other APOE genotypes, and those with the ε4 allele have an earlier age of onset of Alzheimer's disease (Corder et al, 1993;de-Andrade, Larrandaburu, Callegari-Jacques, Gastaldo, & Hutz, 2000;Isbir et al, 2001;Mayeux et al, 1993). APOE ε4 also is associated with greater deposition of beta-amyloid protein in the brains of adults with and without Down syndrome (Hyman, West, Rebeck, Lai, & Mann, 1995), and as for the typically developing population, increased risk for Alzheimer's disease has been associated with the presence of an ε4 allele (Deb et al, 2000;Prasher, Chowdhury, Rowe, & Bain, 1997;Schupf et al, 1996). The presence of an APOE ε4 allele has also been related to increased overall risk of mortality for adults with Down syndrome without Alzheimer's disease , and it may be associated with intellectual decline during early adulthood (Del Bo et al, 1997).…”

Impact of amyloid imaging on drug development in Alzheimer's disease

“…While Aβ plaques are one of the characteristic features of AD confirmed by post mortem evaluation (Fig 1), Aβ deposition in the brain is not unique to clinically apparent AD and also has been found in normal aging, prompting the suggestion that there is a presymptomatic stage of AD [11,12]. Although the time course of Aβ deposition in normal subjects who go on to develop AD has not been fully elucidated, evidence gained through post mortem study of Down syndrome (a condition in which Aβ deposition is always present by age 40 and dementia is very common) suggests that Aβ deposition begins over a decade prior to the clinical symptoms of dementia [13]. Aβ deposition is believed to begin in normal elderly subjects, who subsequently may develop signs of mild cognitive impairment (MCI), and then may finally develop AD (Figs 3 and 4), in whom post mortem analysis demonstrates the characteristic abundance of Aβ plaques in specific brain areas.…”

“…This suggests that effective anti-amyloid therapy should be initiated early in the pathological process of AD in order to be optimally effective. Evidence suggests that Aβ pathology begins a decade or more before clinical symptoms are apparent [13]. Imaging technologies such as [ 11 C]PiB that can detect Aβ deposits are under development by several groups [16,90,91,92].…”