ALZHEIMER'S DISEASE CENTER CORE GRANT

dementia has reached epidemic proportions in our aging society, and most
affected are thought to have Alzheimer's Disease (AD). Clinical
diagnostic accuracy is only about 80% and neuropathological diagnosis
presents some difficulty. The cause of D is unknown. It is suspected
that AD is heterogeneous. There are also overlaps of AD with Parkinson's
disease and vascular dementia. The objectives of this proposal are to
apply objective clinical measures to more accurately diagnose AD and to
follow these patients and controls in a longitudinal study. Clinical data
will be correlated with neuropathological analysis. A patient data base
(patient registry) and tissue repository (brain bank) will support these
studies. Three major clinical research projects concern heterogeneity: one will
assess the extrapyramidal subtype using clinical, electrophysiological and
biochemical measures; a related pilot project assesses postural control
and vestibular function measures as diagnostic tools for this subtype and
another pilot explores new probes for dopamine-2 receptors as another
biochemical tool. Another major clinical project investigates genetic
heterogeneity by HLA markers. The third clinical project applies
hemorheological methods to study the role of the cerebral circulation in
AD and vascular dementia. These research efforts are aimed at better
understanding different patient populations with subtypes of AD and the
different factors which may contribute to the cause. Both clinical and
biochemical markers may therefore not only provide a better means of
diagnosis but may eventually result in understanding etiology and therapy.
Another pilot is aimed at developing better immunochemical probes for
beta-amyloid which may be useful in diagnosis and for assessing the
potential existence of abnormal forms of the protein in AD as a possible
basic mechanism in causality. Another pilot, purely basic in design,
examines the role of glutamine in memory mechanisms in the rat hippocampus
by studying the influence of cholinergic inputs on excitatory synaptic
transmission in dissociated cultures of hippocampus with voltage and patch
clamp techniques. In addition to the above, a beginning is made to study possible
ameliorative therapies in a pilot project which evaluates bright light or
melatonin administration as possible treatment for disturbance in
sleep/wake cycles in AD. There is also a therapeutic feasibility trial
using synvinolin (an analog of lovastatin which lowers cholesterol) in AD
and vascular dementia who have rheological abnormalities.