Harvard University

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.

Beta-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease.

B J Cummings; C J Pike; R Shankle; C W Cotman (Profiled Author: Cotman, Carl W)

Laboratory for Molecular Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02178, USA. cummings@helix.mgh.harvard.edu
Neurobiology of aging 1996;17(6):921-33.

The relationship between progressive cognitive decline and underlying neuropathology associated with Alzheimer s disease (AD) is a key issue in defining the mechanisms responsible for functional loss. This has been a subject of much controversy, with separate studies comparing various clinical and neuropathological indices in AD. Further, it is difficult to compare studies with differences in histochemical staining protocols, brain regions examined, and data quantification criteria. There are many difficulties in designing a clinical-pathological correlative study involving AD patients. It is necessary to control for several key parameters. For example, a broad range of cognitively impaired subjects is needed, as well as short postmortem delays, brief intervals between cognitive testing and death, and the most sensitive detection and quantification techniques. In this study, we carefully controlled for each of these parameters to determine if there is a relationship between global cognitive dysfunction and multiple neuropathological indices. We selected 20 individuals representing a broad range of cognitive ability from normal to severely impaired based on the MMSE, Blessed IMC, and CDR. We counted plaque number, NFT number, dystrophic neurite number, and the relative extent of thioflavine positive plaques and neuritic involvement within plaques. We also quantified cortical area occupied by beta-amyloid immunoreactivity (A beta Load) and PHF-1 positive neuropil threads and tangles (PHF Load) using computer-based image analysis. Interestingly, we found that most pathologic measures correlated highly with the severity of dementia. However, the strongest predictor of premortem cognitive dysfunction on all three cognitive measures was the relative area of entorhinal cortex occupied by beta-amyloid deposition. In conclusion, our data show that in a carefully controlled correlative study, a variety of neuropathological variables are strongly correlated with cognitive impairment. Plaque related variables may be as strongly related to cognitive dysfunction as other established measures, including synapse loss, cell death and tau hyperphosphorylation, although no correlative study can demonstrate causality.

2 Originating Grant

• 1.

  COTMAN, CARL WAYNE

  Behavior and Neural Plasticity in the Aged

  1 August 1997 - 31 March 2013

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 30,822,252

• 2.

  COTMAN, CARL W

  MECHANISMS AND MOLECULAR PROFILES OF DEGENERATION IN AD

  25 May 1995 - 30 April 2001

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 1,154,804

Scientific Context

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