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

D. Iacono, W. R. Markesbery, M. Gross, O. Pletnikova, G. Rudow, P. Zandi, J. C. Troncoso

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)665-673
Number of pages9
Issue number9
StatePublished - Sep 1 2009


Dive into the research topics of 'The Nun Study: Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life'. Together they form a unique fingerprint.

Cite this