Project: Research project


The broad objectives of this proposal are: (l) to determine when the amyloid P component is incorporated into the
intracellular and extracellular brain lesions of Alzheimer's disease. (2) to investigate the potential in vivo sequelae of microinjection of the
amyloid P component, obtained from Alzheimer neural tissues into rodent
brains at different ages. The first objective will be carried out by single- and double-antigen
immunohistochemistry in brains from Alzheimer patients and neurologically
intact aged controls. Each Alzheimer brain will be carefully staged by
histopathological methods to determine the severity of degeneration both
at the gross, regional and microscopic lesion levels. Thereafter, the
immunolabeling of the amyloid P component will be compared by quantitative
stereological methods to early and late markers of Alzheimer lesions. The
integrity of the neural defense mechanisms (both intra- and extracellular)
and the microenvironment surrounding the deposits of the amyloid P
component will also be investigated. Results from the first objective will
point out when the amyloid P component becomes incorporated during the
temporal sequence of Alzheimer lesion formation and whether its presence
in the brain correlates to changes in the integrity of brain defense
mechanisms and microenvironment. The second objective of this study will be carried out by microinjection
of amyloid P component in the rodent brain at different ages. The amyloid
P component used in these experiments will be extracted and purified from
Alzheimer brains. Control animals will receive either amyloid P component
obtained from normal aged brains or the carrier solution which will be
Tris-saline. Following selected survival periods of up to 6 months, the
fate of the amyloid P component deposit and its effects on the surrounding
brain cells and microenvironment will be determined by quantitative
stereological methods. This portion of the study will focus on the
potential brain clearance mechanisms of the amyloid P component deposits
and the effects of age on the efficiency of these mechanisms. The proposed study will add to our understanding of the potential
etiological role of the amyloid P component in the process of Alzheimer
lesion formation. Systematic study of the role played by each component of
Alzheimer lesions will allow for future therapeutic strategies.
Effective start/end date5/1/944/30/00


  • National Institutes of Health
  • National Institutes of Health: $97,673.00
  • National Institutes of Health
  • National Institutes of Health: $58,829.00
  • National Institutes of Health: $57,243.00


Serum Amyloid P-Component
Alzheimer Disease
Defense Mechanisms
Cellular Microenvironment


  • Medicine(all)
  • Neuroscience(all)