Neurodegeneration in Normal Brain Aging and Disease

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  • Dietmar Rudolf Thal
    Dietmar R. Thal is in the Department of Neuropathology at the University of Bonn Medical Center, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. Kelly Del Tredici and Heiko Braak are at the Institute for Clinical Neuroanatomy at Johann Wolfgang Goethe University, D-60590 Frankfurt am Main, Germany.(D.R.T.)
  • Kelly Del Tredici
    Dietmar R. Thal is in the Department of Neuropathology at the University of Bonn Medical Center, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. Kelly Del Tredici and Heiko Braak are at the Institute for Clinical Neuroanatomy at Johann Wolfgang Goethe University, D-60590 Frankfurt am Main, Germany.(D.R.T.)
  • Heiko Braak
    Dietmar R. Thal is in the Department of Neuropathology at the University of Bonn Medical Center, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. Kelly Del Tredici and Heiko Braak are at the Institute for Clinical Neuroanatomy at Johann Wolfgang Goethe University, D-60590 Frankfurt am Main, Germany.(D.R.T.)

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<jats:p>Normal "healthy" aging is defined as aging without disease. Many aged people do not exhibit symptoms of disease and lead normal lives, but nonetheless display pathological changes that are characteristic of Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and/or cerebrovascular disease (CVD). These changes are restricted to distinct brain regions and might represent preclinical stages of these disorders. This Perspective discusses arguments in favor of and against the hypothesis that pathological changes related to AD, PD, DLB, and CVD in the brains of nondemented elderly people represent early stages of these diseases rather than healthy aging. We conclude that early pathological disease-related changes do indeed constitute the beginning of AD, PD, DLB, and CVD rather than normal concomitants of aging, even in the absence of any clinical symptoms. Aging is, therefore, a major risk factor for these diseases but does not necessarily lead to age-related diseases.</jats:p>

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