Perry, Elaine K

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.

Accumulation of pathological tau species and memory loss in a conditional model of tauopathy.

Zdenek Berger; Hanno Roder; Amanda Hanna; Aaron Carlson; Vijayaraghavan Rangachari; Mei Yue; Zbigniew Wszolek; Karen Ashe; Joshua Knight; Dennis Dickson; et al. (Profiled Authors: Dickson, Dennis; Hutton, Michael)

Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2007;27(14):3650-62.

Neurofibrillary tangles (NFTs) are a pathological hallmark of Alzheimer's disease and other tauopathies, but recent studies in a conditional mouse model of tauopathy (rTg4510) have suggested that NFT formation can be dissociated from memory loss and neurodegeneration. This suggests that NFTs are not the major neurotoxic tau species, at least during the early stages of pathogenesis. To identify other neurotoxic tau protein species, we performed biochemical analyses on brain tissues from the rTg4510 mouse model and then correlated the levels of these tau proteins with memory loss. We describe the identification and characterization of two forms of tau multimers (140 and 170 kDa), whose molecular weight suggests an oligomeric aggregate, that accumulate early in the pathogenic cascade in this mouse model. Similar tau multimers were detected in a second mouse model of tauopathy (JNPL3) and in tissue from patients with Alzheimer's disease and FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17). Moreover, levels of the tau multimers correlated consistently with memory loss at various ages in the rTg4510 mouse model. Our findings suggest that accumulation of early-stage aggregated tau species, before the formation of NFT, is associated with the development of functional deficits during the pathogenic progression of tauopathy.

7 Originating Grant

• 1.

  Dickson, Dennis William

  Genetics and Molecular Biology of Parkinsonism

  30 September 1999 - 31 August 2009

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

  Total Funding: $ 8,904,777

• 2.

  Dickson, Dennis W

  GENETICS AND MOLECULAR BIOLOGY OF PARKINSONISM

  30 September 1999 - 29 September 2004

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

  Total Funding: $ 2,454,521

• 3.

  Hardy, John A

  GENETICS AND MOLECULAR BIOLOGY OF PARKINSONISM

  30 September 1999 - 31 July 2004

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

  Total Funding: $ 3,886,270

• 4.

  Dickson, Dennis William

  Tau and Neurodegeneration II: A therapeutic target

  1 September 1999 - 31 May 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 4,182,608

• 5.

  Hutton, Michael L

  Tau and Neurodegeneration II: A therapeutic target

  1 September 1999 - 31 May 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 8,997,034

• 6.

  MUFSON, ELLIOTT JAY

  Neurobiology of Mild Cognitive Impairment in the Elderly

  1 September 1997 - 31 March 2013

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 20,516,366

• 7.

  BENNETT, DAVID ALAN

  Rush Alzheimer's Disease Core Center

  15 August 1997 - 30 June 2016

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 20,028,581

Scientific Context

This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.