Spatial memory deficiency early in 6xTg Alzheimer's disease mouse model

Scientific Reports
Shinwoo KangKeun-A Chang

Abstract

Alzheimer's disease (AD) is mainly characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFTs). While the recent 5xFAD AD mouse model exhibits many AD-related phenotypes and a relatively early and aggressive amyloid β production, it does not show NFTs. Here, we developed and evaluated a novel AD mouse model (6xTg-AD, 6xTg) by crossbreeding 5xFAD mice with mice expressing mutant (P301L) tau protein (MAPT). Through behavioral and histopathological tests, we analyzed cognitive changes and neuropathology in 6xTg mice compared to their respective parental strains according to age. Spatial memory deficits occurred in 6xTg mice at 2 months of age, earlier than they occurred in 5xFAD mice. Histopathological data revealed aggressive Aβ42 and p-tau accumulation in 6xTg mice. Microglial activation occurred in the cortex and hippocampus of 6xTg mice beginning at 2 months. In 6xTg model mice, the synaptic loss was observed in the cortex from 4 months of age and in the hippocampus from 6 months of age, and neuronal loss appeared in the cortex from 4 months of age and in the hippocampus 6 months of age, earlier than it is observed in the 5xFAD and JNPL3 models. These result...Continue Reading

References

Apr 10, 1992·Science·J Hardy, G A Higgins
Aug 25, 2001·Annual Review of Neuroscience·V M LeeJohn Q Trojanowski
Sep 26, 2003·The American Journal of Pathology·Eric FalkeSteven E Arnold
Dec 4, 2003·Neurobiology of Aging·Salvatore OddoFrank M LaFerla
Sep 29, 2009·Neurobiology of Disease·Fiona GrueningerLaurence Ozmen
Oct 1, 2013·Neurobiology of Disease·Céline HéraudJean-Pierre Brion
Mar 8, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ilie-Cosmin StancuIlse Dewachter
Mar 31, 2016·EMBO Molecular Medicine·Dennis J Selkoe, John Hardy
Mar 1, 2015·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Giovanni A CarlesimoGianfranco Spalletta
Oct 18, 2016·The European Journal of Neuroscience·Rosemary J JacksonTara L Spires-Jones
Dec 28, 2016·Acta Neuropathologica·Eleanor Drummond, Thomas Wisniewski
Aug 5, 2017·The EMBO Journal·Hiroki SasaguriTakaomi C Saido
Oct 14, 2017·Nature Reviews. Neurology·J WangYan-Jiang Wang
Jun 14, 2018·Nature Reviews. Neurology·Erin E Congdon, Einar M Sigurdsson
Sep 12, 2018·Journal of Neuroscience Research·Danielle BeckmanJohn H Morrison
Oct 9, 2018·European Journal of Medicinal Chemistry·Young-Do KwonHee-Kwon Kim
Nov 9, 2018·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Jefferson W KinneyBruce T Lamb
Jul 19, 2020·International Journal of Molecular Sciences·Eunjoo NamKeun-A Chang

Methods Mentioned

BETA
protein assay
biopsy
ELISA
transgenic
X-ray

Related Concepts

Alzheimer's Disease
Cerebral Cortex
Hippocampus (Brain)
Crossbreeding
Laboratory mice
Synapses
Neurofibrillary Degeneration (Morphologic Abnormality)
Tau Proteins
Amyloid beta-protein (1-42)
Intracellular

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