Dr. Galasko currently serves as Interim Director of the UCSD Shiley-Marcos Alzheimer's Disease Research Center (ADRC). Dr. Galasko has made important original research contributions in the area of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Specific areas of investigation include biological markers and genetic risk factors for AD, heterogeneity in AD, and subtypes and variants such as DLB. He has also been active in improving clinical measurement in AD, especially indices of progression.
A major area of research activity examines biological markers for AD in cerebrospinal fluid (CSF), cells, and blood. A biological marker for AD would enhance accurate early diagnosis and could also be used to evaluate therapy. Dr. Galasko continues to work on studies involving tau (t) (a microtubule-associated protein that forms neurofibrillary tangles in AD) and has shown that it is increased in CSF in AD and that Ab42 (a peptide that aggregates to form amyloid deposits in the brain and may be neurotoxic in AD) is decreased.
He was the Principal Clinical Investigator in a multi-center study that confirmed the utility of t and b42, showing that a combination of these two markers was more sensitive and specific for AD than either one alone. Most important, this study provided the first evidence of an association between the apolipoprotein E e4 allele (APO-E e4), a genetic risk factor for AD, and lower levels of CSF Ab42. This work led to the publication of a first-author paper in the Archives of Neurology. He is currently examining the relationship between t and Ab42 in CSF and plasma and rate of change in AD, and looking at novel biomarkers related to oxidation and inflammation.
As an investigator at the ADRC, Dr. Galasko has a pivotal role in organizing and coordinating DNA banking, and genotyping for APO-E. He has contributed significant clinical and genetic data to the largest study conducted to date on APO-E, a meta-analysis showing that e4/e4 homozygotes carry a much greater risk than e4 heterozygotes that peak by about age 70 and then decrease. He provided clinical data and tissue for studies that identified polymorphisms in APO-E that alter levels of mRNA of APO-E. These studies showed that polymorphisms in promoter regions of APO-E that lead to increased levels of mRNA expression of APO-E e4 increase the risk of AD. This work has been described in a variety of publications, including JAMA.
In other work, Dr. Galasko has identified and characterized families with very early onset AD and other dementias. He and colleagues have identified four new novel mutations in Presenilin 1. He is currently examining sibling pairs with AD in genome-wide searches to identify new genes related to AD. Dr. Galasko also continues long-term studies on DLB. Together with other project investigators, he was able to show that dementia progression is faster in DLB than in AD, and that a pattern of performance suggestive of subcortical dementia can be discerned in DLB even on global psychometric tests. He has published extensively in this area of research and is routinely invited to international conferences on AD and DLB.
Dr. Galasko developed a much-needed assessment instrument for activities of daily living (ADL) as part of an Alzheimer's Disease Cooperative Study (ADCS) instrument development protocol. The ADL instrument is fine-tuned and able to discriminate excellently among different levels of severity of AD and to capture longitudinal change. The success of this new instrument is clearly evident in its use in eight industry-sponsored multi-center AD clinical trials and four ADCS trials.
In an additional key role, Dr. Galasko is an investigator in the Clinical Core of a NIA-funded study of neurodegenerative diseases in Micronesia. This project examines the Parkinson's-dementia complex in the Chamorro people of Guam. He spends one-month per year in Guam performing research evaluations on a group of about 30 subjects.
Dr. Galasko provides formal courses and lectures as well as individual instruction to medical students, residents, and fellows in a variety of settings, including the inpatient service and several outpatient clinics at the UCSD and VA San Diego Medical Centers. Dr. Galasko regularly reviews articles for a variety of journals, including the Annals of Neurology, Neurology, and American Journal of Psychiatry. He has also served as a reviewer for a number of federal and private granting agencies.
Dr. Galasko’s clinical duties represent approximately 550 hours per annum and include weekly visits to an outpatient neurology clinic (focusing on memory disorders and unusual dementias), attending at the VAMC at the Neurodegenerative Disease/MS Clinic twice per month, and covering sessions at the VA Neurology or Residents Clinic. He regularly receives referrals from other neurologists in San Diego.