Alzheimer's disease: size class frequency distribution of senile plaques: do they indicate when a brain tissue was affected?

Armstrong, Richard A.; Myers, D.; Smith, C. U. M.

doi:10.1016/0304-3940(91)90799-y

Cited by 17 publications

(13 citation statements)

References 18 publications

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“…In accord with previous observations, we found that the profile of plaque sizes when plotted as a function ofA along a linear axis is far from being Gaussian but instead is skewed to the right (13,24,25) (Fig. 2a).…”

Section: Methodssupporting

confidence: 92%

Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

Hyman

West

Rebeck

et al. 1995

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

194

105

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The discovery that the E4 allele of the apolipoprotein E (apoE) gene is a putative risk factor for Alzheimer disease (AD) in the general population has highlighted the role of genetic influences in this extremely common and disabling illness. It has long been recognized that another genetic abnormality, trisomy 21 (Down syndrome), is associated with early and severe development of AD neuropathological lesions. It remains a challenge, however, to understand how these facts relate to the pathological changes in the brains of AD patients. We used computerized image analysis to examine the size distribution of one of the characteristic neuropathological lesions in AD, deposits of AP3 peptide in senile plaques (SPs). Surprisingly, we find that a log-normal distribution fits the SP size distribution quite well, motivating a porous model of SP morphogenesis. We then analyzed SP size distribution curves in genotypically defined subgroups of AD patients. The data demonstrate that both apoE £4/AD and trisomy 21/AD lead to increased amyloid deposition, but by apparently different mechanisms. The size distribution curve is shifted toward larger plaques in trisomy 21/AD, probably reflecting increased AP production. In apoE £4/AD, the size distribution is unchanged but the number of SP is increased compared to apoE E3, suggesting increased probability of SP initiation. These results demonstrate that subgroups of AD patients defined on the basis of molecular characteristics have quantitatively different neuropathological phenotypes.

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Section: Methodssupporting

confidence: 92%

Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

Hyman

West

Rebeck

et al. 1995

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

194

105

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“…This could be attributable to p/A4 deposition occurring earlier in the PHG than the frontal cortex. There is evidence that AD pathology may begin in the temporal lobe and spread to other regions of the cortex [ 19]. However, it could also be due to factors which may enhance amyloid formation in some brain regions.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Differences in β/A4 Protein Subtypes in the Parahippocampal Gyrus and Frontal Cortex in Alzheimer's Disease

Armstrong

1994

Dement Geriatr Cogn Disord

Self Cite

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The density of diffuse, primitive and classic β/A4 protein deposits was estimated in sulci and gyri in the frontal cortex and parahippocampal gyrus (PHG) in 8 cases of Alzheimer''s disease. Total β/A4 deposit density was similar in the frontal cortex and PHG but the ratio of primitive and classic deposits to the total was greater in the PHG compared with the frontal cortex. Total β/A4 deposit density was greater in the depths of the sulci, but the proportions of the various β/A4 subtypes were similar in sulci and gyri. Hence, increased density of primitive and classic deposits in the PHG could reflect enhanced conversion of diffuse to mature deposits whereas increased density of mature β/A4 subtypes in sulci versus gyri may reflect increased β/A4 deposition in the sulci.

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“…Studies suggest that pathological proteins in various neurodegenerative disorders may spread through the brain via anatomical connections [7,30,57]. In AD, for example, this spread frequently occurs from an origin in the medial temporal lobe to the cortical association areas and hippocampus, and then to the primary sensory areas [8,25,49]. Pathogenic TDP-43 may also exhibit this property, and therefore changes in density with duration in specific areas could reflect this spread.…”

Section: Discussionmentioning

confidence: 99%

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables

Armstrong

2016

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A b s t r a c t Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND) but increased with Alzheimer's disease (AD) or hippocampal sclerosis (HS) co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI) while increased survival was associated with greater densities of enlarged neurons (EN) in the frontal and temporal lobes. The data suggest that: (1) survival in FTLD-

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Alzheimer's disease: size class frequency distribution of senile plaques: do they indicate when a brain tissue was affected?

Cited by 17 publications

References 18 publications

Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

Quantitative Differences in β/A4 Protein Subtypes in the Parahippocampal Gyrus and Frontal Cortex in Alzheimer's Disease

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables

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