# SYNAPTIC PLASTICITY DURING AGING AND ALZHEIMER'S DISEASE

> **NIH NIH R01** · MCGILL UNIVERSITY · 1992 · $70,890

## Abstract

One of the most intriguing features of brain aging is the tremendous
variability in the loss of cognitive function and plasticity.  Certain
individuals function alertly up to 90 years of age whereas others show
decline of intellectual ability as their mid-50's and in the extreme form,
develop clinical dementia such as Alzheimer's disease.  What are the
factors that might account for the loss of plasticity and cognitive
functions in the aging brain and, what role(s) do they play in the
impressive individual variation observed during aging in human and rodent:

We are examining molecular mechanisms involved in the CNS reinnervation
process that might regulate the abnormal compensatory plasticity reported
in brain aging and in Alzheimer's disease.  We recently showed that the
brain has evolved a powerful mechanism allowing lipid recycling from
degenerating neurons to reinnervating ones.  This process relies on the
synthesis of apolipoprotein E by astrocytes (for lipid transport) and, the
up-regulation of its receptor (LDL receptor) by neurons.  Preliminary data
indicates that this recycling pathway is compromised in patients with
Alzheimer's disease and, in lesioned rat exposed to glucocorticoid levels
similar to those measured in aged rats.  Studies proposed here will
examined a) the role played by the LDL receptor during normal reinnervation
process in young rats and, b) how it regulates cholesterol synthesis and
storage in brain cells.  We will also attempt to relate changes in
hypothalamic-pituitary-adrenal (HPA) function (glucocorticoid status) to
individual differences in hippocampal synaptic plasticity in later life
using animal models of both "successful aging" (low corticosterone level
and absence of cognitive decline) and "unsuccessful aging" (high cort level
and presence of cognitive decline).  We anticipate to demonstrate a
relationship between the loss of cognitive function in aged rats and a
glucocorticoids-mediated, cholesterol-recycling-dependent reduction of
hippocampal synaptic plasticity.  We hope to show that changes in HPA
function can be used to predict individual differences in cholesterol
recycling and hippocampal plasticity in aged rats.  Finally, we will
examine whether the loss of apolipoprotein E expression observed in the
hippocampus of AD relates to the reported absence of synaptic plasticity in
these patients.  We will also examine the possibility that cholesterol
synthesis and re-uptake could be up-regulated by local hippocampal neurons
to compensate for the loss of apolipoprotein E expression.  These
experiments will allow us to go beyond the variable of chronological age,
and examine some of the factors possibly responsible for a decreased
synaptic plasticity associated with aging and Alzheimer's disease.

## Key facts

- **NIH application ID:** 3121959
- **Project number:** 1R01AG010003-01A1
- **Recipient organization:** MCGILL UNIVERSITY
- **SAM.gov UEI:** VJ62F6V2LE48
- **Principal Investigator:** JUDES POIRIER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $70,890
- **Award type:** 1
- **Project period:** 1992-09-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121959

## Citation

> US National Institutes of Health, RePORTER application 3121959, SYNAPTIC PLASTICITY DURING AGING AND ALZHEIMER'S DISEASE (1R01AG010003-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121959. Licensed CC0.

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