scholarly journals Brain region‐specific amyloid plaque‐associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer’s disease mice

2020 ◽  
Vol 154 (1) ◽  
pp. 84-98 ◽  
Author(s):  
Ibrahim Kaya ◽  
Eva Jennische ◽  
Stefan Lange ◽  
Ahmet Tarik Baykal ◽  
Per Malmberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Myelin Sheath ◽  
Brain Region ◽  
Amyloid Plaque ◽  
Familial Alzheimer’S Disease ◽  
Myelin Lipid ◽  
Familial Alzheimer's Disease

scholarly journals Transcriptome analyses of 7-day-old zebrafish larvae possessing a familial Alzheimer’s disease-like mutation in psen1 indicate effects on oxidative phosphorylation, ECM and MCM functions, and iron homeostasis

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yang Dong ◽  
Morgan Newman ◽  
Stephen M. Pederson ◽  
Karissa Barthelson ◽  
Nhi Hin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidative Phosphorylation ◽  
Transcriptome Analysis ◽  
Iron Homeostasis ◽  
Late Onset ◽  
Wild Type ◽  
Familial Alzheimer’S Disease ◽  
Zebrafish Larvae ◽  
Familial Alzheimer's Disease

Abstract Background Early-onset familial Alzheimer’s disease (EOfAD) is promoted by dominant mutations, enabling the study of Alzheimer’s disease (AD) pathogenic mechanisms through generation of EOfAD-like mutations in animal models. In a previous study, we generated an EOfAD-like mutation, psen1Q96_K97del, in zebrafish and performed transcriptome analysis comparing entire brains from 6-month-old wild type and heterozygous mutant fish. We identified predicted effects on mitochondrial function and endolysosomal acidification. Here we aimed to determine whether similar effects occur in 7 day post fertilization (dpf) zebrafish larvae that might be exploited in screening of chemical libraries to find ameliorative drugs. Results We generated clutches of wild type and heterozygous psen1Q96_K97del 7 dpf larvae using a paired-mating strategy to reduce extraneous genetic variation before performing a comparative transcriptome analysis. We identified 228 differentially expressed genes and performed various bioinformatics analyses to predict cellular functions. Conclusions Our analyses predicted a significant effect on oxidative phosphorylation, consistent with our earlier observations of predicted effects on ATP synthesis in adult heterozygous psen1Q96_K97del brains. The dysregulation of minichromosome maintenance protein complex (MCM) genes strongly contributed to predicted effects on DNA replication and the cell cycle and may explain earlier observations of genome instability due to PSEN1 mutation. The upregulation of crystallin gene expression may be a response to defective activity of mutant Psen1 protein in endolysosomal acidification. Genes related to extracellular matrix (ECM) were downregulated, consistent with previous studies of EOfAD mutant iPSC neurons and postmortem late onset AD brains. Also, changes in expression of genes controlling iron ion transport were observed without identifiable changes in the prevalence of transcripts containing iron responsive elements (IREs) in their 3′ untranslated regions (UTRs). These changes may, therefore, predispose to the apparent iron dyshomeostasis previously observed in 6-month-old heterozygous psen1Q96_K97del EOfAD-like mutant brains.

230 Genetic study of familial Alzheimer's disease in Eastern Finland

1996 ◽  
Vol 17 (4) ◽  
pp. S58
Author(s):  
M. Lehtovirta ◽  
S. Helisalmi ◽  
A. Mannermaa ◽  
M. Ryynänen ◽  
P. Riekkinen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Study ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease ◽  
Eastern Finland

ApoE genotype and familial Alzheimer's disease: a possible influence on age of onset in APP717 Val → Ile mutated families

1995 ◽  
Vol 183 (1-2) ◽  
pp. 1-3 ◽  
Author(s):  
Benedetta Nacmias ◽  
Stefania Latorraca ◽  
Patrizia Piersanti ◽  
Paolo Forleo ◽  
Silvia Piacentini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Age Of Onset ◽  
Apoe Genotype ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease

scholarly journals IC-P-020: A voxel-based morphometry study of volumetric MRI in familial Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_1) ◽  
pp. P17-P18
Author(s):  
David Cash ◽  
Gerard Ridgway ◽  
Natalie Ryan ◽  
Kirsi Kinnunen ◽  
Tom Yeatman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Voxel Based Morphometry ◽  
Volumetric Mri ◽  
Familial Alzheimer’S Disease ◽  
Familial Alzheimer's Disease
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