Sensory cortical mechanisms in Alzheimer's Disease

Project Summary

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder and the most common cause of dementia among the elderly. The pathological development of AD is characterized by progressive impairment of memory and cognitive functions and is accompanied by amyloid plaques and neurofibrillary tangles. While synaptic loss appears to correlate well with the early emergence of cognitive dysfunction in AD patients, the neural basis for the cognitive impairment, in terms of structural and functional properties of cortical circuitry, remains largely unknown. In this project Dr. Zhang will explore the neural basis for AD-related cognitive impairment in a mouse model of AD and determine how the pathological development of AD is accompanied with specific and progressive changes of functional organization of sensory cortices. Fourier intrinsic optical imaging technique will be applied to study functional organization in sensory cortices. This imaging method detects the intrinsic deoxyhemoglobin signals which indicate brain activity (with a spatial resolution of 30-50 micrometers), and allows to locate cortical regions activated by specific sensory stimuli within a large-scale cortical area. Therefore, by applying various sensory stimuli, Dr. Zhang can visualize how cortical representation of these stimuli is topographically organized. In addition, Fourier-based analysis allows a rapid acquisition of results. In fact, a similar paradigm used in this technique can also be extended to functional MRI for imaging human cortex, since both detect similar intrinsic signals. This project represents an initial effort in investigating the neural basis underlying the cognitive impairment in AD. By comparing cortical functional organization between AD and normal aging sensory cortex, and by monitoring changes of cortical functional organization during the pathological development of AD, a better understanding can be established of the neural basis underlying the functional deficits caused by AD. This study may also have impact on early diagnosis of AD.