BIOLOGY OF HEREDITARY PRP AMYLOIDOSIS WITH TANGLES

Project: Research project

Project Details

Description

A large Indiana kindred is affected by an autosomal dominant neurologic
disorder. The disease of the Indiana kindred is characterized clinically
by cerebral ataxia, parkinsonism and dementia, and pathologically by
amyloid plaques, neuritic plaques, neurofibrillary tangles (as in Alzheimer
disease), nerve-cell loss and presence of iron deposits in the striatum and
substantia nigra. Abnormal eye movements are present early in the disease
and may precede onset of neurologic signs. Amyloid of plaques is not
recognized by polyclonal antibodies against the Alzheimer disease beta-
protein, but does contain epitopes recognized by antibodies against a prion
protein (PrP). However, unlike PrP-positive cases of Gerstmann-Straussler-
Scheinker syndrome, in which there are mutations in the open reading frame
(ORF) of the PrP gene, no putative disease-causing mutation has been found
in the PrP ORF of the Indiana kindred. We postulate that the disease of
the Indiana kindred is a distinct entity that shares clinical and
pathologic similarities with Gerstmann-Straussler-Scheinker syndrome on the
one hand and with Alzheimer disease on the other. Our overall goal is to expand and correlate information on several aspects
of the Indiana kindred, each relevant to a Program Project to be developed
within the next three years. We propose to: (I) Conduct prospective
clinical and brain magnetic resonance imaging to clarify the natural
history of the disease; (II) Define the ocular motor functions in at-risk
and affected subjects; (III) Continue defining the pathology of the Indiana
kindred; (IV) Biochemically characterize the amyloid of the Indiana kindred
and (V) Determine the chromosomal map position of the disease-causing gene. The study of this neurodegenerative process will contribute to the
understanding of the basic mechanisms operating in central nervous system
amyloidogenesis and neurofibrillary tangle formation.
StatusFinished
Effective start/end date7/1/916/30/99

Funding

  • National Institutes of Health: $389,327.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $178,374.00
  • National Institutes of Health: $554,176.00
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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