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- Title
Characterization of a Mouse Model of Alzheimer's Disease Expressing Aβ4-42 and Human Mutant Tau.
- Authors
Zampar, Silvia; Wirths, Oliver; Rostagno, Agueda A.; Baranowska-Bik, Agnieszka; Orzechowski, Arkadiusz
- Abstract
The relationship between the two most prominent neuropathological hallmarks of Alzheimer's Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence places Aβ upstream in the cascade of pathological events, triggering NFTs formation and the subsequent neuron loss. Extracellular Aβ deposits were indeed causative of an increased tau phosphorylation and accumulation in several transgenic models but the contribution of soluble Aβ peptides is still controversial. Among the different Aβ variants, the N-terminally truncated peptide Aβ4–42 is among the most abundant. To understand whether soluble Aβ4–42 peptides impact the onset or extent of tau pathology, we have crossed the homozygous Tg4–42 mouse model of AD, exclusively expressing Aβ4–42 peptides, with the PS19 (P301S) tau transgenic model. Behavioral assessment showed that the resulting double-transgenic line presented a partial worsening of motor performance and spatial memory deficits in the aged group. While an increased loss of distal CA1 pyramidal neurons was detected in young mice, no significant alterations in hippocampal tau phosphorylation were observed in immunohistochemical analyses.
- Subjects
NEUROFIBRILLARY tangles; LABORATORY mice; ALZHEIMER'S disease; ANIMAL disease models; PYRAMIDAL neurons; BEHAVIORAL assessment; TAU proteins
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 10, p5191
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22105191