Affiliations: [a] Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia | [b] Neural Plasticity and Regeneration Group, Neuroscience Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia | Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA
Correspondence:
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Corresponding author: Dr. J. Götz, Alzheimer's and Parkinson's Disease Laboratory, Brain and Mind Research Institute, University of Sydney, 100 Mallett St, Camperdown, NSW 2050, Australia. Tel.: +61 2 9351 0789; Fax: +61 2 9351 0731; E-mail: [email protected].
Abstract: Neurodegenerative diseases are characterized by 'hot spots' of degeneration. The regions of primary vulnerability vary between different neurodegenerative diseases. Within these regions, some neurons are lost whereas others that are morphologically indiscriminate survive. The enigma of this selective vulnerability is tightly linked to two fundamental problems in the neurosciences. First, it is not understood how many neuronal cell types make up the mammalian brain; estimates are in the order of more than a thousand. Second, the mechanisms by which some nerve cells undergo functional impairment followed by degeneration while others do not, remain elusive. Understanding the basis for this selective vulnerability has significant implications for understanding the pathogenesis of disease and for developing treatments. Here, we review what is known about selective vulnerability in Alzheimer's disease, frontotemporal dementia, and Parkinson's disease. We suggest, since transgenic animal models of disease reproduce aspects of selective vulnerability, that these models offer a valuable system for future investigations into the physiological basis of selective vulnerability.
