Monitoring Alzheimer's Disease

Gerry Shaw, PhD
University of Florida (Gainesville, FL)
Year Awarded:
2009
Grant Duration:
April 1, 2009 to March 31, 2012
Disease:
Alzheimer's Disease
Award Amount:
$150,000
Grant Reference ID:
A2009315
Award Type:
Pilot
Award Region:
US Southern
Partially supported by a generous donation from the Kenneth and Ann Reim Trust

Blood And CSF Biomarkers Of Alzheimer's Disease

Summary

Alzheimer's disease is difficult to diagnose and it is also difficult to monitor the progression of the disease. We have developed two assays which can be used to monitor neurodegeneration using blood and cerebrospinal fluid (CSF) samples. The aim of the present proposal is to see if these assays can be used to monitor Alzheimer's disease.

Details

Alzheimer's disease is difficult to diagnose and it is also difficult to monitor the progression of the disease. Monitoring disease progression in a convenient fashion would allow the effectiveness of Alzheimer's disease therapies to be assessed in individual patients, which might be very beneficial. We have developed two assays which can be used to monitor neurodegeneration using blood and cerebrospinal fluid (CSF) samples. The aim of this project is to see if these assays, and modified assays based on them, can be used to specifically monitor the presence and progression of Alzheimer's disease.

Research Updates

We have made a start to this project by performing analyses on three different sources of blood and cerebro-spinal fluid (CSF) samples from patients whose identities are not known to us. Due to Institutional Review Board (IRB) confidentiality requirements, we are not able to present the results of our experiments in full detail. This will be done after a full collection of samples have been analyzed in Gainesville and all the data is provided to the partner institutions, who will then break the code and allow us to interpret our findings with the information provided on the disease condition of the patients. Preliminary data decoded to date reveal the following points:
  1. A cohort of patient samples collected in London show that the levels of UCHL1 protein in CSF are elevated not only in Alzheimer's disease (AD), but also in Creutzfeld-Jacob's Disease, diffuse Lewy body disease, frontotemporal dementia, Parkinson's disease (PD) and progressive supranuclear palsy. This suggests that this protein is, as expected, a general marker of neuronal loss in neurodegenerative diseases, but also, as expected, not specific for AD.

  2. Long-term studies of apparently healthy, aged individuals have revealed a slight age related increase in the level of blood pNF-H protein. This finding can be explained in one of three ways: either a small and increasing amount of pNF-H protein leaks into the blood in normal adults as a function of aging, or there may concurrent and unrecognized neurological disorders some of our control individuals, or these results may reflect random fluctuations which appear significant due to low sample numbers. Analysis of further groups of patients and controls will solve this problem.

  3. Our ongoing search for novel biomarkers of CNS injury and neural degeneration has produced several new candidate proteins, which are being followed-up aggressively. We have also generated a sensitive and specific enzyme-linked immunosorbent assay (ELISA) test for detecting the presence of alpha-synuclein which we will use on AD patient samples. We have recently used this assay to show that patients with PD as a group have higher blood levels of alpha-synuclein than age matched controls and that a subset of PD patients with the highest blood levels of alpha-synuclein are those with the worst presentation and rate of disease progression. Interestingly, a group of AD patients showed lower average blood levels of alpha-synuclein compared to age matched controls. These findings may allow differentiation of PD patients from those with AD.
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