Early Senile Plaques in Down's Syndrome Brains Show a Close Relationship With Cell Bodies of Neurons

Allsop, David; Haga, S.; Haga, Chie; Ikeda, Shu‐ichi; Mann, David; Ishii, Tsuyoshi

doi:10.1111/j.1365-2990.1989.tb01252.x

Cited by 76 publications

(42 citation statements)

References 28 publications

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“…4). Consistent with prior observations, in both human and canine brains, diffuse deposits often surrounded several unstained areas that contained morphologically normal neuronal cell bodies (2,8). Cerebrovascular amyloid was present in one of the animals (PB2) and deposits were immunoreactive with 10D5, 7A3, and anti-A~340.…”

Section: Resultssupporting

confidence: 70%

Carboxy terminal of β-amyloid deposits in aged human, canine, and polar bear brains

Tekirian

Cole

Russell

et al. 1996

Neurobiology of Aging

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terminal of ~-amyloid deposits in human, canine, and polar bear brains. NEUROBIOL AGING 17(2) 249-257, 1996.--Immunocytochemistry, using antibodies specific for different carboxy termini of AI340 and AI342(43), was used to compare [3-amyloid deposits in aged animal models to nondemented and demented Alzheimer's disease human cases. Aged beagle dogs exhibit diffuse plaques in the absence of neurofibrillary pathology and the aged polar bear brains contain diffuse plaques and PHF-l-positiw~ neurofibrillary tangles. The brains of nondemented human subjects displayed abundant diffuse plaques, whereas the AD cases had both diffuse and mature (cored) neuritic plaques. Diffuse plaques were positively immunostained with an antibody against A[342(43) in all examined species, whereas AI340 immunopositive mature plaques were observed only in the human brain. Anti-Al~40 strongly immunolabeled cerebrovascular [3-amyloid deposits in each of the species examined, although some deposits in the polar bear brain were preferentially labeled with anti-A[342(43). [3-Amyloid deposition was evident in the outer molecular layer of the dentate gyrus in the aged dog, polar bear, and human. Within this layer, A1342 was present as diffuse deposits, although these deposits were morphologically distinct in each of the examined animal models. In dogs, A[342 was cloud-like in nature; the polar bear demonstrated a more aggregated type of deposition, and the nondemented human displayed well-defined deposits. Alzheimer's disease cases were most frequently marked by neuritic plaques in this region. Taken together, the data indicate that 13-amyloid deposition in aged mammals is similar to the earliest stages observed in human brain. In each species, AI342(43) is the initially deposited isoform in diffuse plaques.

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Section: Resultssupporting

confidence: 70%

Carboxy terminal of β-amyloid deposits in aged human, canine, and polar bear brains

Tekirian

Cole

Russell

et al. 1996

Neurobiology of Aging

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“…The morphology and size of SP are highly variable and are regionally dependent (6). Recent studies have addressed the pathogenetic role of neurons, astrocytes, microglia, and capillaries in the development of SP (7)(8)(9)(10)(11). Another prominent lesion of AD is the accumulation of straight and paired helical filaments in neuronal cell bodies and in neurites (12).…”

mentioning

confidence: 99%

Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.

Cras

Kawai

Lowery

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

260

151

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Senile plaques are polymorphous P-amyloid protein deposits found in the brain in Alzheimer disease and normal aging. This .3-amyloid protein is derived from a larger precursor molecule of which neurons are the principal producers in brain. We found that amyloid precursor protein (APP)-immunoreactive neurites were involved in senile plaques and that only a subset of these neurites showed markers for the abnormal filaments characteristic ofneurofibrillary pathology. In the neocortex of nondemented individuals with senile plaques but spared of neurofibrillary pathology, dystrophic neurites in senile plaques showed only APP accumulation. In contrast, in the brains of Alzheimer patients, virtually all APP-immunoreactive neurites also showed immunoreactivity with ubiquitin, x, and phosphorylated neurofilaments. The presence of X and neurofrlament epitopes in dystrophic neurites in senile plaques was correlated with the extent of neurofibrillary pathology in the surrounding brain tissue. Accumulation of APP and the formation of neurofibrillary pathology in senile plaque neurites are therefore distinct phenomena. Our findings suggest that APP accumulation in senile plaque neurites occurs prior to X accumulation and is therefore more closely related to appearance of neuritic dystrophy.Senile plaques (SP) are extracellular amyloid deposits found in the brain most prominently in Alzheimer disease (AD) but also in normal aging (1). Their 6-to 10-nm-wide filaments consist of a 39-to 42-amino acid f3-amyloid protein (f3-AP) (2), which is derived from a much larger transmembrane amyloid precursor protein (APP) (3-5). The morphology and size of SP are highly variable and are regionally dependent (6). Recent studies have addressed the pathogenetic role of neurons, astrocytes, microglia, and capillaries in the development of SP (7-11). Another prominent lesion of AD is the accumulation of straight and paired helical filaments in neuronal cell bodies and in neurites (12). Studies of Down syndrome patients, who invariably develop pathology like that in AD, have shown that amyloid is probably deposited before any neurofibrillary pathology occurs (13). The most frequent form of dystrophic neurites in AD are neuropil threads that are not confined to the SP (14). Furthermore, neuropil threads are also found in progressive supranuclear palsy (15) and subacute sclerosing panencephalitis (16) APP has been localized to cell processes that were tentatively identified as neurites in AD brains (20-23). We reported previously that APP-positive cell processes occur in the absence of M-AP deposits, in diffuse SP, as well as in fully developed f3-AP core-containing plaques (24). These findings suggested that APP accumulation in cell processes could contribute to the deposition of f3-AP in SP.The present study was undertaken to define the cellular origin of APP-immunostained cell processes in SP and to define their relationship to neurofibrillary pathology in AD and normal aging. MATERIAL AND METHODSWe studied the hippocampus and the temp...

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“…Hence, this process may be similar to that of the formation of diffuse β-amyloid (Aβ) deposits observed in Alzheimer's disease (AD) [5,9]. In both AD and Down's syndrome (DS), diffuse Aβ deposits are closely associated with the presence of neuronal cell bodies and may have developed from Aβ secreted from clusters of adjacent neurons [1,3,8,32].…”

Section: Discussionmentioning

confidence: 97%

Original article Spatial relationships between diffuse prion protein deposits and neuronal perikarya in variant Creutzfeldt-Jakob disease

Armstrong¹

2013

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Early Senile Plaques in Down's Syndrome Brains Show a Close Relationship With Cell Bodies of Neurons

Cited by 76 publications

References 28 publications

Carboxy terminal of β-amyloid deposits in aged human, canine, and polar bear brains

Carboxy terminal of β-amyloid deposits in aged human, canine, and polar bear brains

Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.

Original article Spatial relationships between diffuse prion protein deposits and neuronal perikarya in variant Creutzfeldt-Jakob disease

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