The broad goal of my lab is to elucidate the pathophysiological mechanisms underlying neurodegenerative disorders such as Alzheimer’s disease and other dementias by developing and using novel animal models in parallel with studies from affected human subjects.
The LaFerla laboratory has a long-standing interest in understanding how co-morbidities influence the onset and progression of Alzheimer’s disease. Sporadic AD patients typically display 2 to 8 different comorbid conditions, and it is possible that these concomitant medical conditions influence the progression of AD. Among the diversity of the different co-morbid conditions, the lab has focused on three: ischemia/stroke, stress and diabetes. Our findings have contributed significantly to understanding how stress and ischemia impact AD pathogenesis. Recently, we discovered that type 1 diabetes requires tau to induced synaptic and cognitive impairments. These observations have led us to investigate if the more common form of diabetes (type 2) also requires tau for the manifestation of the cognitive and synaptic impairments and to further explore the underlying molecular mechanisms by which synaptic integrity is compromised by type 1 and 2 diabetes. These studies have led to a better understanding of the molecular connections by which two highly prevalent human disorders are related, which could facilitate the development of novel interventions for AD patients with diabetes.
Inflammation is a fundamental protective response, but if it becomes dysregulated, it can be a major co-factor in the pathogenesis of many chronic human diseases, including Alzheimer disease. My laboratory has made important discoveries as to how inflammatory processes trigger AD pathogenesis (including Ab and tau) and impair cognition. Currently, we are investigating the impact of Ab on IL-1b signaling, with an emphasis on the relevance of protein clearance for IL-1b synthesis and protein trafficking for IL-1R1 levels. The translational impact of this work is substantial and significant, as these studies have uncovered new therapeutic targets for the treatment of AD.