Diabetes increases an individual’s risk of developing AD and other forms of status, exercise status, and type 2 diabetes or impaired fasting glucose. …
COMMONWEALTH OF VIRGINIA
Alzheimers and Related Diseases Research Award Fund
2006-2007 ALZHEIMERS RESEARCH AWARD FUND RECIPIENTS ANNOUNCED
The Alzheimers and Related Diseases Research Award Fund ARDRAF was
established by the Virginia General Assembly in 1982 to stimulate
innovative investigations into Alzheimers disease AD and related
disorders along a variety of avenues, such as the causes, epidemiology,
diagnosis, and treatment of the disorder; public policy and the financing
of care; and the social and psychological impacts of the disease upon the
individual, family, and community The ARDRAF competition is administered
by the Virginia Center on Aging at Virginia Commonwealth University in
Richmond The seven grant awards for 2006-2007 are as follows:
VCU Dusan Bratko, D Sc Department of Chemistry Computer
Screening of Amyloidogenic Protein Variants
Because of its ability to provide microscopic insights not accessible by
experiment, computational chemistry is becoming an important tool in
biophysical and biomedical research This study addresses, through computer
simulation, the molecular properties of pathological intra- or
extracellular
agglomerations of misfolded proteins associated with
Alzheimers and related diseases The role of mutations that affect peptide
aggregation will be inspected as well If successful, the proposed work
will represent a significant step toward the development of high-throughput
computational methods to screen amyloidogenic protein variants This
understanding will assist in identifying systems conditions and protein
mutations relevant for prediction, treatment, and prevention of
debilitating processes involved in neurodegenerative diseases New insights
into these association mechanisms will contribute toward elucidating
fundamental biophysical principles of multi-protein assembly, a key element
for successful control of disease-related aggregation processes
Dr Bratko can be reached at 804/828-1865
EVMS Frank J Castora, PhD Department of Physiological Sciences
Effect of T9861C mtDNA Mutation on Cytochrome Oxidase Structure
and Function
Mitochondria, the powerhouses of cells, play an important role in the
development of Alzheimers Disease AD, and researchers are examining the
mitochondrial DNA molecule for mutations that may be associated with AD
This
investigator has identified a mutation T9861C that dramatically
reduces the activity of cytochrome oxidase, one of the essential components
of the respiratory chain The current project is designed to extend this
preliminary observation by evaluating the activity of cytochrome oxidase in
more AD samples that also possess the same mutation This research will
also use a combination of separation techniques to determine if the
mutation is changing the structure or assembly of the cytochrome oxidase
complex Evaluating the effect of this mutation on the structure and
function of cytochrome oxidase may help identify how disrupting normal
mitochondrial function could lead to or accelerate the development of AD
This, in turn, could provide a potential target for slowing down that
inevitable progression Dr Castora can be reached at 757/ 624-2270
ODU Sheri R Colberg, PhD, FACSM and colleagues Department of
Exercise Science The Relationship among Alzheimers Disease, Dementia,
Diabetes, and Physical Activity Status
Diabetes increases an individuals risk of developing AD and other forms of
dementia eg, vascular, while regular physical activity has been shown
to lower this risk The
purpose of this study, therefore, is to examine
the relationship among cognitive status, exercise status, and type 2
diabetes or impaired fasting glucose The investigators will study 150
people, ages 50-85, half with and the other half without diabetes, using a
battery of tests including two cognitive tests Mini-Mental State Exam and
the St Louis University Mental Status exam, a depression scale the Even
Briefer Assessment Scale for Depression, physical activity Harvard Alumni
Physical Activity Questionnaire and activities of daily living the
Modified Barthel Index questionnaires, and various metabolic tests
fasting insulin, glucose, glycated hemoglobin, C-peptide, cholesterol,
tumor necrosis factor-alpha, and more The primary goal is to determine
whether regular exercisers have a better cognitive status compared with non-
exercisers, and more importantly, if subjects with diabetes who are regular
exercisers have better cognitive function than sedentary diabetic and even
possibly non-diabetic subjects These findings would indicate that the
enhanced risk of developing AD or dementia due to diabetes or impaired
glucose metabolism can be, at least partially if not fully, offset by
the
AD risk reduction conferred by regular physical activityDr Colberg can
be reached at 757/ 683- 4995
UVA Paul Freedman, PhD, Richard J Bonnie, LL B, and
Thomas M Guterbock, PhD Department of Politics; Government
Foreign Affairs Voting and Dementia in Virginia Long-Term Care
Facilities
This group of investigators will study the policies and practices that
affect voting by senior citizens in long-term care settings such as nursing
homes and assisted living facilities, particularly as they bear on the
enfranchisement or disenfranchisement of residents with dementia and
other cognitive impairments The first component of the study is a multi-
mode survey of staff informants from a representative sample of long-term
care facilities in the Commonwealth of Virginia The survey will be
designed to collect data on registration and voting practices, with an
emphasis on the measures taken if any to assess voting capacity of
individuals with diagnoses of dementia, to promote and facilitate voting by
those who are capable of doing so, and to prevent fraudulent exploitation
of those who lack the capacity to vote The second component is a
vote-
validation study, designed to ascertain from public records the
registration status and rate of electoral participation of a sample of
residents from a sub-sample of the surveyed long-term care facilities The
results will indicate which policies and practices are most effective in
facilitating voting by those residents capable of doing so, and provide the
foundation for a national study Dr Freedman can be reached at 434/924-
1372; Professor Bonnie can be reached at 434/ 924-3209
UVA Ian G Macara, PhD and Huaye Zhang, PhD Center for Cell
Signaling, School of Medicine The Role of Septins in
Alzheimers Disease
One of the pathological hallmarks of Alzheimers disease AD is the
formation of neurofibrillary tangles NFTs, twisted tangles inside the
brains nerve cells, which contain hyperphosphorylated tau proteins In
healthy cells, tau is attached to long strands called microtubules, which
act as the cells skeleton However, in the brain cells of AD patients,
tau falls off of the microtubules and sticks together to form tangles In
addition to tau, a family of guanosine triphosphate GTP-binding proteins,
known as septins, is also found in the NFTs
These investigators have
found that septins bind with a homologue of tau that is distributed mainly
in non-neuronal tissues, microtubule-associated protein 4 MAP4, and
induces dissociation of MAP4 from microtubules The major goal of this
research is to elucidate the role that septins play in regulating tau-
microtubule interactions in hippocampal neurons In addition, the study
will test the hypothesis that septins facilitate NFT formation, first in
cultured cells, and then eventually in vivo These results will provide
new insights into the function of septins in neuronal cells and their role
in Alzheimers disease Dr Macara can be reached at 434/924-1236
GMU Jeanne Sorrell, PhD, RN College of Nursing and Health and
Catherine J Tompkins, PhD Department of Social Work Ethics
of Respect for Spirituality in Persons Living with Alzheimers
Disease
This study seeks to answer the question, How do members of a faith
community describe experiences of spiritual connections to Alzheimers
disease AD? The investigators will implement a grounded theory
methodology to explore the concepts that comprise spiritual pathways and
identify categories of
spiritual connections within the social context of
persons with AD and their families living in a faith community
Unstructured interviews with persons diagnosed with AD, family caregivers,
and members of five faith communities will elicit in-depth descriptions of
participants experiences in three primary focus areas: 1 spiritual
beliefs related to coping with AD for both persons with AD and caregivers,
both in the early and late stages of the disease, 2 ways in which
spirituality contributes to the overall concept of quality of life within a
faith community, and 3 ways in which members of faith communities
facilitate or hinder the development of spiritual connects for persons with
AD and their families Qualitative data will be analyzed to identify
codes, concepts, and categories relevant to the spiritual dimensions that
characterize participants experiences Implications of an ethics of
respect for spirituality in persons living with AD will be discussed in
terms of their implications for health care practice, education, research,
and policy Dr Sorrell can be reached at 703/993-1944; Dr Tompkins can
be reached at 703/ 993-2838
VCU Jeffrey L Dupree, PhD
Department of Anatomy and
Neurobiology Understanding the Role of Sulfatide in
Maintaining Viable Neurons in Alzheimers Disease
Since neuronal death is the most prevalent pathology in AD, most research
has focused on understanding intra-neuronal processes that regulate
survival This project, however, will investigate a class of cells whose
role in maintaining viable adult neurons has been grossly ignored, ie,
the supporting glial cells known as oligodendrocytes OLGs, best known for
their role in the formation of myelin, the insulating wrap that ensures
rapid nerve impulse transmission In addition, they are almost exclusively
responsible for the production of a prominent brain lipid, known as
sulfatide, which is significantly reduced in the earliest stages of
dementia The investigator has recently used a mouse that is unable to
synthesize sulfatide to show that this lipid is required for the
maintenance of oligodendrocyte-neuron interactions The loss of proper OLG-
neuron communication induces abnormal tau phosphorylation as seen in AD
In the aged sulfatide null mice, the accumulation of hyperphosphorylated
tau results in a collapse of the microtubular
network and the formation of
neurofibrillary tangles, one of the hallmark features of AD This
investigator is primarily interested in the initial events that alter tau
phosphorylation, and hypothesizes that the loss of OLG-neuronal
interactions is one of the unknown external insults that activates tau-
directed kinases and contributes to AD pathogenesis The funded study will
test this hypothesis by analylzing the accumulation of hyperphosphorylated
tau and determining changes in the expression and distributution of
specific tau kinases implicated in AD Dr Dupree can be reached at
804/828-9536
