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.

Aberrant phosphoinositide metabolism in Alzheimer's disease.

S Shimohama; S Fujimoto; N Tresser; P Richey; G Perry; P J Whitehouse; Y Homma; T Takenawa; T Taniguchi; T Suenaga (Profiled Authors: Whitehouse, Peter J; Perry, George)

Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
Annals of the New York Academy of Sciences 1993;695():46-9.

Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, its involvement was assessed in Alzheimer's disease (AD). The phosphatidyl-inositol (PI)-specific PLC activity in the Alzheimer cytosolic and particulate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in AD. Immunostaining of a specific antibody against the PLC isozyme, PLC-delta, demonstrated that this enzyme was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores, and neuropil threads in AD brains. Western blot analysis confirmed that PLC-delta was concentrated in the paired helical filament (PHF)-rich fraction of AD brains. PLC-delta marked the same neurons containing tau immunoreactivity and yet tau and PLC-delta often marked different structures within the same neuron, with tau more clearly on NFT and PLC-delta covering it superficially. The double stain with PLC-delta and basic fibroblast growth factor (bFGF) binding suggest that PLC-delta is an intracellular marker, showing little overlap with bFGF binding, an extracellular marker. All of this was consistent with the electron microscopy, with PLC-delta being NFT associated. Antibodies to other PLC isozymes did not produce positive immunostaining of these pathologic structures. Moreover, diffuse and amorphous deposits of PLC-delta were found to precede the accumulation of fibrillary deposits. These results suggest that PLC-delta accumulation plays a possible role in the formation of intraneuronal inclusions in AD.

2 Originating Grant

• 1.

  PERRY, GEORGE

  NEUROFIBRILLARY PATHOLOGY IN ALZHEIMER DISEASE

  1 September 1990 - 30 November 2000

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 1,191,333

• 2.

  PERRY, GEORGE

  AMYLOID PRECURSOR IN ALZHEIMERS DISEASE

  1 April 1988 - 30 June 1995

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 536,600

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.