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July 8, 2009

The Nun Study
Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life

September 1, 2009 issue
73 (9) 665-673

Abstract

Background: It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic β-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered.
Methods: Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups.
Results: A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups.
Conclusions: 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.

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Information & Authors

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Published In

Neurology®
Volume 73Number 9September 1, 2009
Pages: 665-673
PubMed: 19587326

Publication History

Published online: July 8, 2009
Published in print: September 1, 2009

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Affiliations & Disclosures

D. Iacono, MD, PhD
From the Departments of Pathology (D.I., O.P., G.R., J.C.T.), Division of Neuropathology, Neurology (J.C.T.), and Mental Health (P.Z.), Johns Hopkins University, Baltimore, MD; Departments of Pathology, Neurology, and Alzheimer’s Disease Center (W.R.M.), Sanders-Brown Center on Aging, University of Kentucky, Lexington; and Department of Laboratory Medicine and Pathology (M.G.), University of Minnesota, Minneapolis.
W. R. Markesbery, MD
From the Departments of Pathology (D.I., O.P., G.R., J.C.T.), Division of Neuropathology, Neurology (J.C.T.), and Mental Health (P.Z.), Johns Hopkins University, Baltimore, MD; Departments of Pathology, Neurology, and Alzheimer’s Disease Center (W.R.M.), Sanders-Brown Center on Aging, University of Kentucky, Lexington; and Department of Laboratory Medicine and Pathology (M.G.), University of Minnesota, Minneapolis.
M. Gross, PhD
From the Departments of Pathology (D.I., O.P., G.R., J.C.T.), Division of Neuropathology, Neurology (J.C.T.), and Mental Health (P.Z.), Johns Hopkins University, Baltimore, MD; Departments of Pathology, Neurology, and Alzheimer’s Disease Center (W.R.M.), Sanders-Brown Center on Aging, University of Kentucky, Lexington; and Department of Laboratory Medicine and Pathology (M.G.), University of Minnesota, Minneapolis.
O. Pletnikova, MD
From the Departments of Pathology (D.I., O.P., G.R., J.C.T.), Division of Neuropathology, Neurology (J.C.T.), and Mental Health (P.Z.), Johns Hopkins University, Baltimore, MD; Departments of Pathology, Neurology, and Alzheimer’s Disease Center (W.R.M.), Sanders-Brown Center on Aging, University of Kentucky, Lexington; and Department of Laboratory Medicine and Pathology (M.G.), University of Minnesota, Minneapolis.
G. Rudow, BS
From the Departments of Pathology (D.I., O.P., G.R., J.C.T.), Division of Neuropathology, Neurology (J.C.T.), and Mental Health (P.Z.), Johns Hopkins University, Baltimore, MD; Departments of Pathology, Neurology, and Alzheimer’s Disease Center (W.R.M.), Sanders-Brown Center on Aging, University of Kentucky, Lexington; and Department of Laboratory Medicine and Pathology (M.G.), University of Minnesota, Minneapolis.
P. Zandi, PhD
From the Departments of Pathology (D.I., O.P., G.R., J.C.T.), Division of Neuropathology, Neurology (J.C.T.), and Mental Health (P.Z.), Johns Hopkins University, Baltimore, MD; Departments of Pathology, Neurology, and Alzheimer’s Disease Center (W.R.M.), Sanders-Brown Center on Aging, University of Kentucky, Lexington; and Department of Laboratory Medicine and Pathology (M.G.), University of Minnesota, Minneapolis.
J. C. Troncoso, MD
From the Departments of Pathology (D.I., O.P., G.R., J.C.T.), Division of Neuropathology, Neurology (J.C.T.), and Mental Health (P.Z.), Johns Hopkins University, Baltimore, MD; Departments of Pathology, Neurology, and Alzheimer’s Disease Center (W.R.M.), Sanders-Brown Center on Aging, University of Kentucky, Lexington; and Department of Laboratory Medicine and Pathology (M.G.), University of Minnesota, Minneapolis.

Notes

Address correspondence and reprint requests to Dr. Juan C. Troncoso, Division of Neuropathology, Department of Pathology, Johns Hopkins University, School of Medicine, Ross Building 558, 720 Rutland Avenue, Baltimore, MD 21205 [email protected]

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