# MEMBRANE CHANGES IN NEUROLOGIC AND AGING DISEASES

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 1993 · $190,307

## Abstract

The purpose of this proposal is to investigate the role of band 3 and
senescent cell antigen (SCA), an aging antigen that is a degradation
product of band 3, in neurological aging and disease.  Since SCA is
intimately involved in cellular aging and removal, we will elucidate its
role in neural aging and disease.  We will begin by investigating band 3
structure and function in adult and aging brain.  We will determine whether
it undergoes the same age related changes as the anion transporter, "band
3," in other cells.  The following anion transporter, band 3, changes are
observed with cellular aging:  increased degradation detected by
immunoblotting with band 3 antibodies, decreased anion transport activity
(increased Km; decreased Vmax), decreased number of high affinity ankyrin
binding sites, and binding of physiologic IgG autoantibodies in situ (1-
27).  In addition, the anion transporter, band 3, undergoes an as yet
undefined change that results in binding of "980" antibodies to aged band
3.  We will quantitate the amount of SCA IgG and amount of SCA on neural
tissue of various ages.  Kinetic studies will be performed on pieces of
perfused brains obtained immediately and at various time intervals
following death to determine whether there is an increase in SCA following
cell death.  Titers of antibodies to band 3, synthetic peptides of band 3
and SCA will be determined with ELISA in both serum and cerebral spinal
fluid (CSF) to determine if antibodies are present to promote phagocytosis
of neurons by glial cells.  Mice will be used for the initial aging
studies.  However, results will be tested in parallel experiments on human
tissue.  We will compare the changes in neurological diseases such as
Alzheimer's Disease (AD) to those occurring during normal brain aging.  We
continue working on and characterizing 5 antibodies we have that
distinguish between normal human brain tissue and tissue from individuals
with AD.  The specific aims of the proposed research are:  1. Determine
band 3 structural and functional changes during brain aging.  2. Quantitate
brain band 3, altered band 3, and aging antigen content during aging.  3.
Mechanism of band 3 alterations in aging.  4. Determine whether differences
in serum and CSF antibodies to brain band 3 synthetic peptides and SCA are
detected between young and old normal individuals (both mice and humans).
5. Determine whether differences in serum and CSF antibodies to brain band
3 peptides and SCA are detected between normal individuals and those with
diseases such as Alzheimer's disease, multiple sclerosis, Huntington's
chorea, and age-matched controls.  6. Develop monospecific and monoclonal
antibodies to SCA, aged band 3, and breakdown products of band 3 for
immunoblots, immunohistochemistry, immunoelectron microscopy, and affinity
chromatography.  7. Identify structural and functional alterations in band
3 in neurological diseases such as AD.  8. Quantitate brain band 3, altered
band 3, and aging anti...

## Key facts

- **NIH application ID:** 3120065
- **Project number:** 5R01AG008444-06
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **SAM.gov UEI:** ED44Y3W6P7B9
- **Principal Investigator:** MARGUERITE M KAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $190,307
- **Award type:** 5
- **Project period:** 1989-07-12 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120065

## Citation

> US National Institutes of Health, RePORTER application 3120065, MEMBRANE CHANGES IN NEUROLOGIC AND AGING DISEASES (5R01AG008444-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120065. Licensed CC0.

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