This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (138)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Alzheimer Disease  • Alert me on articles by topic  Social Bookmarking   What's this?

Joseph L. Price, DPhil; Andy I. Ko, BA; Marcus J. Wade, BA; Sarah K. Tsou; Daniel W. McKeel, MD; John C. Morris, MD

Arch Neurol. 2001;58:1395-1402.

Objectives  To determine whether nondemented subjects with pathological evidence of preclinical Alzheimer disease (AD) demonstrate neuronal loss in the entorhinal cortex and hippocampus, and whether the onset of cognitive deficits in AD coincides with the onset of neuronal degeneration.

Methods  Preclinical AD cases have been defined by the absence of cognitive decline but with neuropathological evidence of AD. The hippocampus and entorhinal cortex were examined in 13 nondemented cases (Clinical Dementia Rating [CDR] 0) with healthy brains, 4 cases with preclinical AD, 8 cases with very mild symptomatic AD (CDR 0.5), and 4 cases with severe AD (CDR 3, hippocampus only). The volume and number of neurons were determined stereologically in 2 areas that are vulnerable to AD—the entorhinal cortex (as a whole and layer II alone) and hippocampal field CA1.

Results  There was no significant decrease in neuron number or volume with age in the healthy nondemented group and little or none between the healthy and preclinical AD groups. Substantial decreases were found in the very mild AD group in neuron number (35% in the entorhinal cortex, 50% in layer II, and 46% in CA1) and volume (28% in the entorhinal cortex, 21% in layer II, and 29% in CA1). Greater decrements were observed in CA1 in the severe AD group.

Conclusions  There is little or no neuronal loss in aging or preclinical AD but substantial loss in very mild AD. The findings indicate that AD results in clinical deficits only when it produces significant neuronal loss.

From the Departments of Anatomy and Neurobiology (Dr Price, Messrs Ko and Wade, and Ms Tsou), Pathology and Immunology (Drs McKeel and Morris), and Neurology (Dr Morris) and the Alzheimer's Disease Research Center (Drs Price, McKeel, and Morris), Washington University School of Medicine, St Louis, Mo.

Corresponding author and reprints: Joseph L. Price, DPhil, Department of Anatomy and Neurobiology, Campus Box 8108, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110 (e-mail: PriceJ{at}Thalamus.wustl.edu).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED ARTICLE

Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2001;58(9):1503-1504.
FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

MRI and CSF biomarkers in normal, MCI, and AD subjects: Diagnostic discrimination and cognitive correlations
Vemuri et al.
Neurology 2009;73:287-293.
ABSTRACT | FULL TEXT  

MRI and CSF biomarkers in normal, MCI, and AD subjects: Predicting future clinical change
Vemuri et al.
Neurology 2009;73:294-301.
ABSTRACT | FULL TEXT  

Visual object pattern separation deficits in nondemented older adults
Toner et al.
Learn. Mem. 2009;16:338-342.
ABSTRACT | FULL TEXT  

Angiotensin II AT2 Receptor Oligomers Mediate G-protein Dysfunction in an Animal Model of Alzheimer Disease
AbdAlla et al.
J. Biol. Chem. 2009;284:6554-6565.
ABSTRACT | FULL TEXT  

Medial temporal lobe atrophy on MRI differentiates Alzheimer's disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis
Burton et al.
Brain 2009;132:195-203.
ABSTRACT | FULL TEXT  

Neuronal Apoptosis and Autophagy Cross Talk in Aging PS/APP Mice, a Model of Alzheimer's Disease
Yang et al.
Am. J. Pathol. 2008;173:665-681.
ABSTRACT | FULL TEXT  

A Two-Year Study with Fibrillar {beta}-Amyloid (A{beta}) Immunization in Aged Canines: Effects on Cognitive Function and Brain A{beta}
Head et al.
J. Neurosci. 2008;28:3555-3566.
ABSTRACT | FULL TEXT  

Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment
Scheff et al.
Neurology 2007;68:1501-1508.
ABSTRACT | FULL TEXT  

Cerebrospinal Fluid tau/beta-Amyloid42 Ratio as a Prediction of Cognitive Decline in Nondemented Older Adults
Fagan et al.
Arch Neurol 2007;64:343-349.
ABSTRACT | FULL TEXT  

Testing a test for Alzheimer disease
Bateman and Eidelberg
Neurology 2007;68:482-483.
FULL TEXT  

Familial risk for Alzheimer's disease alters fMRI activation patterns
Bassett et al.
Brain 2006;129:1229-1239.
ABSTRACT | FULL TEXT  

Serotonin 1A receptors in the living brain of Alzheimer's disease patients
Kepe et al.
Proc. Natl. Acad. Sci. USA 2006;103:702-707.
ABSTRACT | FULL TEXT  

Compensatory Changes in the Noradrenergic Nervous System in the Locus Ceruleus and Hippocampus of Postmortem Subjects with Alzheimer's Disease and Dementia with Lewy Bodies
Szot et al.
J. Neurosci. 2006;26:467-478.
ABSTRACT | FULL TEXT  

Antecedent Biomarkers of Alzheimer's Disease: The Adult Children Study
Coats and Morris
J Geriatr Psychiatry Neurol 2005;18:242-244.
ABSTRACT  

Brain Microarray: Finding Needles in Molecular Haystacks
Lewandowski and Small
J. Neurosci. 2005;25:10341-10346.
FULL TEXT  

Frontal-Hippocampal Double Dissociation Between Normal Aging and Alzheimer's Disease
Head et al.
Cereb Cortex 2005;15:732-739.
ABSTRACT | FULL TEXT  

Conversion From Mild Cognitive Impairment to Probable Alzheimer's Disease Predicted by Brain Magnetic Resonance Spectroscopy
Modrego et al.
Am. J. Psychiatry 2005;162:667-675.
ABSTRACT | FULL TEXT  

Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD
Fotenos et al.
Neurology 2005;64:1032-1039.
ABSTRACT | FULL TEXT  

From The Cover: Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging
Small et al.
Proc. Natl. Acad. Sci. USA 2004;101:7181-7186.
ABSTRACT | FULL TEXT  

Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry
Teipel et al.
Brain 2004;127:811-824.
ABSTRACT | FULL TEXT  

Early A{beta} accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain
Ingelsson et al.
Neurology 2004;62:925-931.
ABSTRACT | FULL TEXT  

Morphology of the Inner Structure of the Hippocampal Formation in Alzheimer Disease
Adachi et al.
Am. J. Neuroradiol. 2003;24:1575-1581.
ABSTRACT | FULL TEXT  

Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease
Giannakopoulos et al.
Neurology 2003;60:1495-1500.
ABSTRACT | FULL TEXT  

Caspase Gene Expression in the Brain as a Function of the Clinical Progression of Alzheimer Disease
Pompl et al.
Arch Neurol 2003;60:369-376.
ABSTRACT | FULL TEXT  

White Matter Structural Integrity in Healthy Aging Adults and Patients With Alzheimer Disease: A Magnetic Resonance Imaging Study
Bartzokis et al.
Arch Neurol 2003;60:393-398.
ABSTRACT | FULL TEXT  

Atrophy rates of entorhinal cortex in AD and normal aging
Du et al.
Neurology 2003;60:481-486.
ABSTRACT | FULL TEXT  

Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis
Redwine et al.
Proc. Natl. Acad. Sci. USA 2003;100:1381-1386.
ABSTRACT | FULL TEXT  

MRI measures of entorhinal cortex versus hippocampus in preclinical AD
Morris et al.
Neurology 2002;59:1474-1475.
FULL TEXT  

Natural history of mild cognitive impairment in older persons
Bennett et al.
Neurology 2002;59:198-205.
ABSTRACT | FULL TEXT  

Brain to Plasma Amyloid-beta Efflux: a Measure of Brain Amyloid Burden in a Mouse Model of Alzheimer's Disease
DeMattos et al.
Science 2002;295:2264-2267.
ABSTRACT | FULL TEXT