Abnormal white matter integrity in healthy apolipoprotein E epsilon4 carriers

Apolipoprotein E ϵ4 is a major genetic risk factor for Alzheimer's disease, but the neurobiological basis for this risk is unknown. We used diffusion tensor imaging to measure diffusion anisotropy in the parahippocampal gyrus white matter in healthy elderly apolipoprotein E ϵ4 carriers and noncarriers. We also measured volumes of the lateral ventricles and temporal horns as proxies of cerebral atrophy. The ϵ4 carriers (n=14) showed significantly lower fractional anisotropy and higher radial diffusivity in the parahippocampal white matter 15 mm below the anterior commissure–posterior commissure plane than noncarriers (n=15). No group differences in ventricular volumes were found, nor were diffusion tensor imaging measures modulated by ventricular volumes. Diffusion tensor imaging may be sufficiently sensitive to detect preclinical brain changes related to Alzheimer's disease.

[1]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[2]  Yu-Min Kuo,et al.  Increased Aβ Peptides and Reduced Cholesterol and Myelin Proteins Characterize White Matter Degeneration in Alzheimer's Disease† , 2002 .

[3]  Takashi Yoshiura,et al.  Diffusion tensor in posterior cingulate gyrus: correlation with cognitive decline in Alzheimer's disease , 2002, Neuroreport.

[4]  A. Lajtha,et al.  Effects of Acute Lorazepam Administration on Aminergic Activity in Normal Elderly Subjects: Relationship to Performance Effects and Apolipoprotein Genotype , 2004, Neurochemical Research.

[5]  John Russell,et al.  Dysmyelination Revealed through MRI as Increased Radial (but Unchanged Axial) Diffusion of Water , 2002, NeuroImage.

[6]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[7]  Ian J. Deary,et al.  Cognitive change and the APOE epsilon 4 allele. , 2002 .

[8]  A. Brun,et al.  A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study , 1986, Annals of neurology.

[9]  B. Reisberg,et al.  Diffusion Tensor Imaging of Frontal White Matter Microstructure in Early Alzheimer’s Disease: A Preliminary Study , 2005, Journal of geriatric psychiatry and neurology.

[10]  O. Saitoh,et al.  Quantification of lateral ventricular subdivisions in schizophrenia by high-resolution three-dimensional magnetic resonance imaging , 2003, Psychiatry Research: Neuroimaging.

[11]  H. Braak,et al.  On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer's disease , 2004, Acta Neuropathologica.

[12]  C. DeCarli,et al.  APOE-epsilon4 is associated with less frontal and more medial temporal lobe atrophy in AD. , 1999, Neurology.

[13]  P. Basser,et al.  Water Diffusion Changes in Wallerian Degeneration and Their Dependence on White Matter Architecture , 2000 .

[14]  H. Hanyu,et al.  Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease , 1998, Journal of the Neurological Sciences.

[15]  H. Braak,et al.  Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis , 1996, Acta Neuropathologica.

[16]  M. Pericak-Vance,et al.  Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Douglas Walker,et al.  Increased A beta peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease. , 2002, Biochemistry.

[18]  Charles DeCarli,et al.  APOE-ε4 is associated with less frontal and more medial temporal lobe atrophy in AD , 1999, Neurology.

[19]  S. Resnick,et al.  Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype , 2000, Neurology.

[20]  Matthias J. Müller,et al.  Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study , 2004, Dementia and Geriatric Cognitive Disorders.

[21]  M Takasaki,et al.  Increased water diffusion in cerebral white matter in Alzheimer's disease. , 1997, Gerontology.

[22]  S. Rose,et al.  Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging , 2000, Journal of neurology, neurosurgery, and psychiatry.

[23]  M. Filippi,et al.  White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging , 2002, Journal of neurology, neurosurgery, and psychiatry.

[24]  Sheng-Kwei Song,et al.  Diffusion tensor imaging detects age-dependent white matter changes in a transgenic mouse model with amyloid deposition , 2004, Neurobiology of Disease.

[25]  V. Wedeen,et al.  Reduction of eddy‐current‐induced distortion in diffusion MRI using a twice‐refocused spin echo , 2003, Magnetic resonance in medicine.

[26]  R. Floris,et al.  Diffusion and perfusion MR imaging in cases of Alzheimer's disease: correlations with cortical atrophy and lesion load. , 2001, AJNR. American journal of neuroradiology.

[27]  Caroline Hayward,et al.  Ageing: Cognitive change and the APOE ɛ4 allele , 2002, Nature.

[28]  H. Braak,et al.  High Frequency of Apolipoprotein E ϵ4 Allele in Young Individuals with Very Mild Alzheimer's Disease-Related Neurofibrillary Changes , 1998, Experimental Neurology.