Neuropathologic Studies of the Baltimore Longitudinal Study of Aging (BLSA)

Issue title: Mini-Forum: Clinical-Pathologic Correlations in Population- and Community-Based Studies of Brain Aging

Guest editors: Thomas Montine and Joshua Sonnen

Article type: Research Article

Authors: O'Brien, Richard J.^a | Resnick, Susan M.^b | Zonderman, Alan B.^b | Ferrucci, Luigi^c | Crain, Barbara J.^d | Pletnikova, Olga^d | Rudow, Gay^d | Iacono, Diego^d | Riudavets, Miguel A.^e | Driscoll, Ira^b | Price, Donald L.^d | Martin, Lee J.^d | Troncoso, Juan C.^{a; d; *}

Affiliations: [a] Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA | [b] Laboratory of Personality and Cognition, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA | [c] Clinical Research Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA | [d] Division of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA | [e] FLENI (Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia), Department of Pathology, Buenos Aires, Argentina

Correspondence: [*] Address for correspondence: Juan C. Troncoso, Departments of Pathology & Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA. Tel.: +1 410 955 5632; Fax: +1 410 955 9777; E-mail: [email protected].

Abstract: The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The BLSA is supported by the National Institute of Aging (NIA) and its mission is to learn what happens to people as they get old and how to sort out changes due to aging from those due to disease or other causes. In 1986, an autopsy program combined with comprehensive neurologic and cognitive evaluations was established in collaboration with the Johns Hopkins University Alzheimer's Disease Research Center (ADRC). Since then, 211 subjects have undergone autopsy. Here we review the key clinical neuropathological correlations from this autopsy series. The focus is on the morphological and biochemical changes that occur in normal aging, and the early neuropathological changes of neurodegenerative diseases, especially Alzheimer's disease (AD). We highlight the combined clinical, pathologic, morphometric, and biochemical evidence of asymptomatic AD, a state characterized by normal clinical evaluations in subjects with abundant AD pathology. We conclude that in some individuals, successful cognitive aging results from compensatory mechanisms that occur at the neuronal level (i.e., neuronal hypertrophy and synaptic plasticity) whereas a failure of compensation may culminate in disease.

Keywords: α-synuclein, Alzheimer's disease, asymptomatic Alzheimer's disease, amyloid-β, dementia, Parkinson's disease, stereology, successful aging, tau

DOI: 10.3233/JAD-2009-1179

Journal: Journal of Alzheimer's Disease, vol. 18, no. 3, pp. 665-675, 2009