Mostly separate distributions of CLAC- versus Abeta40- or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of beta-amyloid deposits

Topic: Brain proteins, microglia and lab models

Collagenous Alzheimer amyloid plaque component (CLAC) is a unique non-Abeta amyloid component of senile plaques (SP) derived from a transmembrane collagen termed CLAC-precursor. Here we characterize the chronological and spatial relationship of CLAC with other features of SP amyloid in the brains of patients with Alzheimer's disease (AD), Down syndrome (DS), and of PSAPP transgenic mice. In AD and DS cerebral cortex, CLAC invariably colocalized with Abeta42 but often lacked Abeta40- or thioflavin S (thioS)-reactivities. Immunoelectron microscopy of CLAC-positive SP showed labeling of fibrils that are more loosely dispersed compared to typical amyloid fibrils in CLAC-negative SP. In DS cerebral cortex, diffuse plaques in young patients were negative for CLAC, whereas a subset of SP became CLAC-positive in patients aged 35 to 50 years, before the appearance of Abeta40. In DS cases over 50 years of age, Abeta40-positive SP dramatically increased, whereas CLAC burden remained at a constant level. In PSAPP transgenic mice, CLAC was positive in the diffuse Abeta deposits surrounding huge-cored plaques. Thus, CLAC and Abeta40 or thioS exhibit mostly separate distribution patterns in SP, suggesting that CLAC is a relatively early component of SP in human brains that may have inhibitory effects against the maturation of SP into beta-sheet-rich amyloid deposits.

@article{kowa2004-15215182,
  author  = {Kowa, H. and Sakakura, T. and Matsuura, Y. and Wakabayashi, T. and Mann, D. M. and Duff, K. and Tsuji, S. and Hashimoto, T. and others},
  title   = {{Mostly separate distributions of CLAC- versus Abeta40- or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of beta-amyloid deposits}},
  journal = {The American journal of pathology},
  year    = {2004},
  doi     = {10.1016/s0002-9440(10)63295-6},
  pmid    = {15215182},
  url     = {https://doi.org/10.1016/s0002-9440(10)63295-6}
}

Key findings

• Immunoelectron microscopy of CLAC-positive SP showed labeling of fibrils that are more loosely dispersed compared to typical amyloid fibrils in CLAC-negative SP.
• Thus, CLAC and Abeta40 or thioS exhibit mostly separate distribution patterns in SP, suggesting that CLAC is a relatively early component of SP in human brains that may have inhibitory effects against the maturation of SP into beta-sheet-rich amyloid deposits.

Why it matters

This brain tissue study found that CLAC and Abeta40 or thioflavin S were mostly in separate parts of senile plaques, suggesting CLAC appears early and may slow the maturation of plaques into beta-sheet-rich amyloid. This is laboratory tissue work and does not show a treatment or cure for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/s0002-9440(10)63295-6
• PubMed: 15215182
• Original source →
• Free full text: American Journal Of Pathology →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes Nature medicine · 1998-01-01 · usefulness score 58/100 · Risk genes beyond APOE
• Age-related amyloid beta deposition in transgenic mice overexpressing both Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant is not associated with global neuronal loss The American journal of pathology · 2000-07-01 · usefulness score 49/100 · Risk genes beyond APOE
• Quantitation of apoE domains in Alzheimer disease brain suggests a role for apoE in Abeta aggregation Journal of neuropathology and experimental neurology · 2001-04-01 · usefulness score 41/100 · Genetics

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