Abstract

Because many cell types and disease states exist in the sample of cells in even a very small region of Alzheimer's disease (AD) brain tissue, optimal understanding of disease mechanisms requires study at the level of the single cell. Our Golgi studies of single neurons in the AD brain have revealed reduced dendritic extent in many, but not all, brain regions. This reduced dendritic extent is interpreted as reduced capacity of neurons in AD to proliferate new dendritic material. Studies of message expression in single neurons reveal that neurons containing neurofibrillary tangles (NFTs) show reduced expression of messages for proteins related to growth of neuronal processes and to synapses. Neighboring neurons free of NFTs express these messages at levels approximating the levels expressed by single neurons from control brain. This reduction of expression of messages related to growth of neuronal processes and to synapses is selective, because expression of message for the lysosomal enzyme, cathepsin D, is increased in neurons containing NFTs. Simultaneous analysis of the expression of multiple genes by single neurons using an aRNA technique offers powerful capacity to profile message expression as a function of disease state of single cells.