# PLATELET-ENDOTHELIAL CELL INTERACTIONS IN ALZHEIMER'S

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 1993 · $281,776

## Abstract

Although the characteristic deposits of beta-amyloid protein in the brain
of Alzheimer's Disease (AD) patients were described many years ago, the
discovery that such patients also have beta-amyloid deposits in the
vasculature is more recent.  There is a strong indication that this
proteins's origin is the amyloid precursor protein which has recently been
discovered to be present, in relatively large quantities, in the platelet
alpha-granules.  The mechanism of platelet activation, and subsequent
degranulation, as well as the ways in which this precursor's release in AD
patients differ from those of normal controls, remain unelucidated, as does
the alternative possibility that the platelet activation process and the
precursor protein release are normal but that the processing of the
precursor into the amyloid protein is abnormal.  The origin of this
processing enzyme(s), also remains controversial.  Since the amyloid
deposits are found in the vasculature, the possibility that AD platelets
interact differently with the endothelial cells of the vascular wall must
be considered.  Thus, since deposits of the abnormal degradation product of
APP are found in AD but not in normal patients of comparable age, there may
be a difference in the platelets' APP content, stimulus response,
processing of released products and/or interactions with or in the presence
of endothelial cells.

Based on our extensive experience in the study of early platelet responses
to agonists, we have already begun to investigate the contents, stimulus
response, signal transduction and degranulation of AD and normal age-
matched platelets, with young adults as controls.  In preliminary studies
to date we have been able to demonstrate that AD platelets exhibit normal
resting membrane potentials and cytoplasmic Ca++ concentrations, but low
cytoplasmic pH.  Stimulation with thrombin appears to lead to abnormally
high levels of granule product release, in conjunction with normal membrane
potential and [Ca++] in changes.  The granule release appears to be greater
in AD than in normal platelets in the presence of endothelial cells as
well, and appear to penetrate through that layer when confluent human
umbilical vein endothelial cells are involved; cells with tighter
junctions, better models of the blood brain barrier, are being prepared.
We plan to examine this finding in greater detail, and to use our
multiparameter flow kinetic technique which will permit determination of
several of these platelet-related events simultaneously, in all the cells
or in subpopulations, on very small samples (<1 million cells).  We already
have permission to study a 75 inpatient, 50 out-patient AD population at
the V.A. hospital in Bedford, MA and are getting such permission for the
Boston City Hospital's AD hospice which has more female and minority
patients.

We hope that our studies will delineate differences in AD platelets'
interactions with and/or stimulation responses in the presence of
endothelial ...

## Key facts

- **NIH application ID:** 3122637
- **Project number:** 5R01AG010684-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **SAM.gov UEI:** FBYMGMHW4X95
- **Principal Investigator:** Elizabeth R Simons
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $281,776
- **Award type:** 5
- **Project period:** 1991-09-29 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122637

## Citation

> US National Institutes of Health, RePORTER application 3122637, PLATELET-ENDOTHELIAL CELL INTERACTIONS IN ALZHEIMER'S (5R01AG010684-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122637. Licensed CC0.

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