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Evidence for Subtypes

William Bondareff, MD, PhD; Christopher Q. Mountjoy, FRCPsych(UK); Martin Roth, MD, ScD, FRCP, FRCPsych(UK); Martin N. Rossor, MD, MRCP; Leslie L. Iversen, MA, PhD, FRS; Gavin P. Reynolds, PhD

Arch Gen Psychiatry. 1987;44(5):412-417.

Abstract
• In support of heterogeneity in Alzheimer's disease (AD), the existence of clinical and biologic subtypes has been claimed. We have investigated this claim by a statistical analysis of the relationships between the number of neurons in nucleus locus ceruleus (nLC), cortical levels of neurotransmitters, number of cortical plaques and tangles, and age. We separated AD patients into two groups: AD-1, with a less severe loss of nLC neurons; and AD-2, with a greater loss. The AD-2 cases were associated with less choline acetyltransferase activity, smaller concentrations of somatostatin and norepinephrine, and more plaques and tangles in the cerebral cortex. Although the mean age at death was less and the duration of dementia was greater in AD-2 patients than in AD-1 patients, the differences in these age-related variables were not significant. Further evidence of heterogeneity came from discriminant function analyses based on nLC neuronal counts and age at death. These findings, suggesting two subtypes of AD, suggest heterogeneity.

Author Affiliations
From the Department of Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry, University of Southern California School of Medicine, Los Angeles (Dr Bondareff); Department of Psychiatry, Clinical School (Drs Mountjoy and Roth) and Neurochemical Pharmacology Unit, Medical Research Council Medical School, (Drs Rossor, Iversen, and Reynolds) University of Cambridge, Cambridge, England. Dr Mountjoy is now with St Andrew's Hospital, Northhampton, England; Dr Rossor, St Mary's Hospital, London; Dr Iversen, Neuroscience Research Center, Merck, Sharpe & Dohme, Harlow, England; and Dr Reynolds, Deparment of Pathology, University of Nottingham Medical School, Nottingham, England.

Footnotes
Accepted for publication Sept 12, 1986.

Reprint requests to Department of Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry, University of Southern California Health Science Campus, 2025 Zonal Ave, Los Angeles, CA 90033 (Dr Bondareff).

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