BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice.

BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Research Abstract Details 

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BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Abstract Text:

Masuo Ohno,Sarah L Cole,Marina Yasvoina,Jie Zhao,Martin Citron,Robert Berry,John F Disterhoft,Robert Vassar,

Evidence suggests that beta-amyloid (Abeta) peptide triggers a pathogenic cascade leading to neuronal loss in Alzheimer's disease (AD). However, the causal link between Abeta and neuron death in vivo remains unclear since most animal models fail to recapitulate the dramatic cell loss observed in AD. We have recently developed transgenic mice that overexpress human APP and PS1 with five familial AD mutations (5XFAD mice) and exhibit robust neuron death. Here, we demonstrate that genetic deletion of the beta-secretase (BACE1) not only abrogates Abeta generation and blocks amyloid deposition but also prevents neuron loss found in the cerebral cortex and subiculum, brain regions manifesting the most severe amyloidosis in 5XFAD mice. Importantly, BACE1 gene deletion also rescues memory deficits in 5XFAD mice. Our findings provide strong evidence that Abeta ultimately is responsible for neuron death in AD and validate the therapeutic potential of BACE1-inhibiting approaches for the treatment of AD.

BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Publishing Authors By Initials

M Ohno,SL Cole,M Yasvoina,J Zhao,M Citron,R Berry,JF Disterhoft,R Vassar,

For similar nervous system: neurons research abstracts see: nervous system: neurons research

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BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Neurobiology of disease

VOLUME: 26

Page Numbers: 134-45

Journal Abbreviation: Neurobiol. Dis.

ISSN: 0969-9961

DAY: 20

MONTH: 12

YEAR: 2006

BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Information

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LANGUAGE: eng

NlmUniqueID: 9500169

BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Keywords Mesh Terms:

KEYWORDS: Neurons

MESH TERMS: pathology

Chemical & Substance for Abstract: BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Information

Substance Name: BACE1 protein, human

Registry Number: EC 3.4.23.46

Grant and Affiliation Information for BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice.

AFFILIATION: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3008, USA. mohno@nki.rfmh.org

Country: United States

AGENCY: United States NIA

GRANT: R37 AG08796

ACRONYM: AG

MEDLINETA: Neurobiol Dis

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