Soluble LR11 competes with amyloid β in binding to cerebrospinal fluid–high-density lipoprotein

Yano, Kouji; Hirayama, Satoshi; Misawa, Naomi; Furuta, Ayaka; Ueno, Toshihide; Motoi, Yumiko; Seino, Utako; Ebinuma, Hiroyuki; Ikeuchi, Takeshi; Schneider, Wolfgang J.; Bujo, Hideaki; Miida, Takashi

doi:10.1016/j.cca.2018.11.024

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…There are also indications for its dysfunction in AD brains 34 . Within the homeostatic community 1 , we find an up-regulation of APOE-associated signaling, with higher expression in Astr.1 of APOE, a major AD susceptibility gene 35 , and its putative receptor SORL1 (based on previous reports [36][37][38] ), a susceptibility locus for AD associated with cognitive decline levels 39 , upregulated in homeostatic Micr.1 ( Fig. 6g-i ).…”

Section: Distinct Ligand-receptor Pairs Identified In the Homeostaticsupporting

confidence: 64%

Multi-cellular communities are perturbed in the aging human brain and Alzheimer’s disease

Cain

Taga

McCabe

et al. 2020

Preprint

112

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The role of different cell types and their interactions in Alzheimer’s disease (AD) is an open question that we have pursued by mapping the human brain at the single cell level. Here, we present a high resolution cellular map of the aging frontal cortex by single nucleus RNA-sequencing of 24 individuals with different clinicopathologic characteristics; which we used to infer the cellular architecture of 640 individuals from bulk RNA-seq profiles. Powered by this sample of sufficient size to obtain statistically robust results, we uncovered AD associations with neuronal subtypes and oligodendroglial states. Moreover, we uncovered a network of cellular communities, each composed of different neuronal, glial and endothelial cells subpopulations whose frequencies are correlated across individuals. Two of the cellular communities are altered in relation to cognitive decline and tau pathology. Our work provides a roadmap for evaluating cross-cell type differences in the cellular environment of the AD brain.

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Section: Distinct Ligand-receptor Pairs Identified In the Homeostaticsupporting

confidence: 64%

Multi-cellular communities are perturbed in the aging human brain and Alzheimer’s disease

Cain

Taga

McCabe

et al. 2020

Preprint

112

View full text Add to dashboard Cite

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Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families

et al. 2022

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Background Many families with clinical early-onset Alzheimer’s disease (EOAD) remain genetically unexplained. A combination of genetic factors is not standardly investigated. In addition to monogenic causes, we evaluated the possible polygenic architecture in a large series of families, to assess if genetic testing of familial EOAD could be expanded. Methods Thirty-six pedigrees (77 patients) were ascertained from a larger cohort of patients, with relationships determined by genetic data (exome sequencing data and/or SNP arrays). All families included at least one AD patient with symptom onset <70 years. We evaluated segregating rare variants in known dementia-related genes, and other genes or variants if shared by multiple families. APOE was genotyped and duplications in APP were assessed by targeted test or using SNP array data. We computed polygenic risk scores (PRS) compared with a reference population-based dataset, by imputing SNP arrays or exome sequencing data. Results In eight families, we identified a pathogenic variant, including the genes APP, PSEN1, SORL1, and an unexpected GRN frameshift variant. APOE-ε4 homozygosity was present in eighteen families, showing full segregation with disease in seven families. Eight families harbored a variant of uncertain significance (VUS), of which six included APOE-ε4 homozygous carriers. PRS was not higher in the families combined compared with the population mean (beta 0.05, P = 0.21), with a maximum increase of 0.61 (OR = 1.84) in the GRN family. Subgroup analyses indicated lower PRS in six APP/PSEN1 families compared with the rest (beta −0.22 vs. 0.10; P = 0.009) and lower APOE burden in all eight families with monogenic cause (beta 0.29 vs. 1.15, P = 0.010). Nine families remained without a genetic cause or risk factor identified. Conclusion Besides monogenic causes, we suspect a polygenic disease architecture in multiple families based on APOE and rare VUS. The risk conveyed by PRS is modest across the studied families. Families without any identified risk factor render suitable candidates for further in-depth genetic evaluation.

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Soluble LR11 competes with amyloid β in binding to cerebrospinal fluid–high-density lipoprotein

Cited by 2 publications

References 33 publications

Multi-cellular communities are perturbed in the aging human brain and Alzheimer’s disease

Multi-cellular communities are perturbed in the aging human brain and Alzheimer’s disease

Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families

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