Evidence for a diffusional model of Alzheimer amyloid A4 (β-amyloid) deposition during neuritic plaque formation

Beneš, Francine M.; Reifel, J.L.; Majocha, Ronald E.; Marotta, Charles A.

doi:10.1016/0306-4522(89)90400-4

Cited by 22 publications

(13 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Density gradients of Aß have been observed within classic plaques [41], which suggests the coalescence and condensation of amyloid. However, such gradients could also arise from the diffusion of Aß from a single source.…”

Section: 'Independent Origin' or Stages In 'Life History'?mentioning

confidence: 99%

“…In addition, plaque diameter is positively correlated with the number of embedded neurons [40] supporting a neuronal origin. Secondly, diffuse plaques could have arisen by diffusion of Aß from a single source [41], e.g., from adjacent cell processes [42] or blood vessels [24]. Hence, the number of neurons within a plaque could reflect the mass of Aß and the distance over which it diffused within the parenchyma.…”

Section: Diffuse Plaquesmentioning

confidence: 99%

See 1 more Smart Citation

β-Amyloid Plaques: Stages in Life History or Independent Origin?

Armstrong

1998

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

Several types of discrete β-amyloid (Aβ) deposit or senile plaque have been identified in the brains of individuals with Alzheimer’s disease and Down’s syndrome. The majority of these plaques can be classified into four morphological types: diffuse, primitive, classic and compact. Two hypotheses have been proposed to account for these plaques. Firstly, that the diffuse, primitive, classic and compact plaques develop in sequence and represent stages in the life history of a single plaque type. Secondly, that the different Aβ plaques develop independently and therefore, unique factors are involved in the formation of each type. To attempt to distinguish between these hypotheses, the morphology, ultrastructure, composition, and spatial distribution in the brain of the four types of plaque were compared. Although some primitive plaques may develop from diffuse plaques, the evidence suggests that a unique combination of factors is involved in the pathogenesis of each plaque type and, therefore, supports the hypothesis that the major types of Aβ plaque develop independently.

show abstract

Section: 'Independent Origin' or Stages In 'Life History'?mentioning

confidence: 99%

Section: Diffuse Plaquesmentioning

confidence: 99%

β-Amyloid Plaques: Stages in Life History or Independent Origin?

Armstrong

1998

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

show abstract

“…sequence reported for a plaque amyloid polypeptide (8); the preparation and characterization of the monoclonal antibodies have been described (22,23). Positive plaques were isolated after repeated plating.…”

mentioning

confidence: 99%

Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer disease brain: coding and noncoding regions of the fetal precursor mRNA are expressed in the cortex.

Zain

Salim

Chou

et al. 1988

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

View full text Add to dashboard Cite

To gain insight into factors associated with the excessive accumulation of fi-amyloid in the Alzheimer disease (AD) brain, the present studies were initiated to distinguish between a unique primary structure of the ADspecific amyloid precursor mRNA vis a vis other determinants that may affect amyloid levels. Previous molecular cloning experiments focused on amyloid derived from sources other than AD cases. In the present work, we cloned and characterized amyloid cDNA derived directly from AD brain mRNA. Poly(A) + RNA from AD cortices was used for the preparation of Agtll recombinant cDNA libraries. An insert of 1564 nucleotides was isolated that included the (1-amyloid domain and corresponded to 75% of the coding region and :70% of the 3'-noncoding region of the fetal precursor amyloid cDNA reported by others. On RNA blots, the AD amyloid mRNA consisted of a doublet of 3.2 and 3.4 kilobases. In control and AD cases, the amyloid mRNA levels were nonuniform and were independent of glial-specific mRNA levels. Based on the sequence analysis data, we conclude that a segment of the amyloid gene is expressed in the AD cortex as a high molecular weight precursor mRNA with major coding and 3'-noncoding regions that are identical to the fetal brain gene product.

show abstract

“…In AD and DS, diffuse deposits are spatially correlated with neuronal cell bodies [1,5,42]. Development of diffuse deposits may therefore involve: (1) secretion of Aβ monomers from clusters of adjacent neuronal perikarya, (2) association of Aβ monomers to form more complex oligomers, and (3) formation of an aggregated deposit [5,21]. Further condensation of the deposit and its association with neuritic pathology, in the form of dystrophic neuritis (DN), may then result in the formation of a primitivetype Aβ deposit [4].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies suggest that once initiated, Aβ deposits in AD grow in size over time. First, pseudo colour image processing of Aβ deposits in AD reveal gradients of density consistent with growth from a central point [21]. Second, radioiodinated human Aβ can be deposited experimentally in vitro from a dilute solution onto primi tive and diffuse Aβ deposits causing them to grow [38].…”

mentioning

confidence: 99%

Original article Size frequency distributions of β-amyloid (Aβ) deposits: a comparative study of four neurodegenerative disorders

Armstrong

2012

View full text Add to dashboard Cite

A b s t r a c t Deposition of β-amyloid (Aβ), a 'signature' pathological lesion of Alzheimer's disease (AD), is also characteristic of Down's syndrome (DS), and has been observed in dementia with Lewy bodies (DLB) and corticobasal degeneration (CBD). To determine whether the growth of Aβ deposits was similar in these disorders, the size frequency distributions of the diffuse ('pre-amyloid'), primitive ('neuritic'), and classic ('dense-cored') Aβ deposits were compared in AD, DS, DLB, and CBD. All size distributions had essentially the same shape, i.e., they were unimodal and positively skewed. Mean size of Aβ deposits, however, varied between disorders. Mean diameters of the diffuse, primitive, and classic deposits were greatest in DS, DS and CBD, and DS, respectively, while the smallest deposits, on average, were recorded in DLB. Although the shape of the frequency distributions was approximately log-normal, the model underestimated the frequency of smaller deposits and overestimated the frequency of larger deposits in all disorders. A 'power-law

show abstract

Evidence for a diffusional model of Alzheimer amyloid A4 (β-amyloid) deposition during neuritic plaque formation

Cited by 22 publications

References 9 publications

β-Amyloid Plaques: Stages in Life History or Independent Origin?

β-Amyloid Plaques: Stages in Life History or Independent Origin?

Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer disease brain: coding and noncoding regions of the fetal precursor mRNA are expressed in the cortex.

Original article Size frequency distributions of β-amyloid (Aβ) deposits: a comparative study of four neurodegenerative disorders

Contact Info

Product

Resources

About