Iwatsubo, Takeshi

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins.

D R Borchelt; T Ratovitski; J van Lare; M K Lee; V Gonzales; N A Jenkins; N G Copeland; D L Price; S S Sisodia (Profiled Authors: Price, Donald L; Sisodia, Sangram S)

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Neuron 1997;19(4):939-45.

Missense mutations in two related genes, termed presenilin 1 (PS1) and presenilin 2 (PS2), cause dementia in a subset of early-onset familial Alzheimer's disease (FAD) pedigrees. In a variety of experimental in vitro and in vivo settings, FAD-linked presenilin variants influence the processing of the amyloid precursor protein (APP), leading to elevated levels of the highly fibrillogenic Abeta1-42 peptides that are preferentially deposited in the brains of Alzheimer Disease (AD) patients. In this report, we demonstrate that transgenic animals that coexpress a FAD-linked human PS1 variant (A246E) and a chimeric mouse/human APP harboring mutations linked to Swedish FAD kindreds (APP swe) develop numerous amyloid deposits much earlier than age-matched mice expressing APP swe and wild-type Hu PS1 or APP swe alone. These results provide evidence for the view that one pathogenic mechanism by which FAD-linked mutant PS1 causes AD is to accelerate the rate of beta-amyloid deposition in brain.

6 Originating Grant

• 1.

  Price, Donald L

  Alzheimer's Disease and Animal Models

  15 July 1997 - 31 March 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 44,095,695

• 2.

  ALBERT, MARILYN B

  Johns Hopkins Alzheimer's Disease Research Center

  15 July 1997 - 31 March 2015

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 5,559,946

• 3.

  PRICE, DONALD L

  PRESENILINS IN MODELS OF FAMILIAL ALZHEIMERS DISEASE

  12 March 1997 - 28 February 2002

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 2,001,677

• 4.

  PRICE, DONALD L

  DISORDERS OF AGING--TRANSMITTER SYSTEMS & NEUROTROPHINS

  1 April 1984 - 30 June 1997

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

  Total Funding: $ 10,370,755

• 5.

  PRICE, DONALD L

  THE FOREBRAIN CHOLINERGIC SYSTEM IN HEALTH AND DISEASE

  1 April 1984 - 30 June 1992

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

  Total Funding: $ 4,029,351

• 6.

  Sisodia, Sangram S

  PRESENILINS IN MODELS OF FAMILIAL ALZHEIMERS DISEASE

  Total Funding: $ 1,966,810

Scientific Context

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