Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer’s disease

Background: Although the APOE ε4 allele increases the risk of developing AD, the effects of the ε4 allele on brain atrophy in clinical AD patients are controversial. Objective: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD. Methods: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the ε3/3 allele, one group (n = 46) had the ε3/4 allele, and one group (n = 46) had the ε4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE ε4 allele was also examined. Results: The normalized hippocampal volume was correlated with the number of APOE ε4 alleles (r = −0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE ε4 alleles (r = −0.178, p = 0.037). The number of APOE ε4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale–Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale–Revised attention/concentration score (r = 0.191, p = 0.025). Conclusions: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE ε4 allele on the brains of AD patients may have regional specificity.

[1]  Yutaka Hata,et al.  Automated segmentation of human brain MR images aided by fuzzy information granulation and fuzzy inference , 2000, IEEE Trans. Syst. Man Cybern. Part C.

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

[3]  J. Hodges,et al.  Attention and executive deficits in Alzheimer's disease. A critical review. , 1999, Brain : a journal of neurology.

[4]  E. Mori,et al.  Amygdalar volume and emotional memory in Alzheimer's disease. , 1999, The American journal of psychiatry.

[5]  K. Ishii,et al.  Lack of Association of Apolipoprotein E ε4 Allele Dose with Cerebral Glucose Metabolism in Alzheimer Disease , 1998 .

[6]  S Kobashi,et al.  Frontotemporal dementia and Alzheimer disease: evaluation of cortical atrophy with automated hemispheric surface display generated with MR images. , 1998, Radiology.

[7]  E. Mori,et al.  Medial temporal and whole-brain atrophy in dementia with Lewy bodies , 1998, Neurology.

[8]  Minoru Yasuda,et al.  Apolipoprotein E ε4 Allele and Whole Brain Atrophy in Late-Onset Alzheimer's Disease , 1998 .

[9]  H. Soininen,et al.  Longitudinal SPECT study in Alzheimer’s disease: relation to apolipoprotein E polymorphism , 1998, Journal of neurology, neurosurgery, and psychiatry.

[10]  J. Price,et al.  Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. , 1998, Archives of neurology.

[11]  E G Tangalos,et al.  Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease , 1998, Annals of neurology.

[12]  E G Tangalos,et al.  Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects , 1998, Neurology.

[13]  G. Wilcock,et al.  Reduced cholinergic function in normal and Alzheimer's disease brain is associated with apolipoprotein E4 genotype , 1997, Neuroscience Letters.

[14]  E. Mori,et al.  Medial temporal structures relate to memory impairment in Alzheimer’s disease: an MRI volumetric study , 1997, Journal of neurology, neurosurgery, and psychiatry.

[15]  E. Corder,et al.  No difference in cerebral glucose metabolism in patients with Alzheimer disease and differing apolipoprotein E genotypes. , 1997, Archives of neurology.

[16]  E. Mori,et al.  Premorbid brain size as a determinant of reserve capacity against intellectual decline in Alzheimer's disease. , 1997, The American journal of psychiatry.

[17]  Thomas Arendt,et al.  Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele , 1997, The Journal of Neuroscience.

[18]  J. Haines,et al.  ApoE-4 and Age at Onset of Alzheimer's Disease , 1997, Neurology.

[19]  T. Arendt,et al.  Plastic neuronal remodeling is impaired in patients with Alzheimer's disease carrying apolipoprotein epsilon 4 allele. , 1997, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  K. Blennow,et al.  The apolipoprotein E allele epsilon 4 does not correlate with the number of senile plaques or neurofibrillary tangles in patients with Alzheimer's disease. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[21]  H. Soininen,et al.  SPECT and MRI analysis in Alzheimer's disease: relation to apolipoprotein E epsilon 4 allele. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[22]  E M Wijsman,et al.  Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. , 1996, American journal of human genetics.

[23]  H. Soininen,et al.  Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease , 1996, Neurology.

[24]  B T Hyman,et al.  Clinical and pathological correlates of apolipoprotein E ε4 in Alzheimer's disease , 1996, Annals of neurology.

[25]  H. Soininen,et al.  Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes , 1995, Neuroscience.

[26]  W. März,et al.  Apolipoprotein E polymorphism influences not only cerebral senile plaque load but also Alzheimer-type neurofibrillary tangle formation , 1995, Neuroscience.

[27]  D R Fish,et al.  Methods for normalization of hippocampal volumes measured with MR. , 1995, AJNR. American journal of neuroradiology.

[28]  B. Tycko,et al.  Apolipoprotein E and alzheimer's disease: Ethnic variation in genotypic risks , 1995, Annals of neurology.

[29]  C. Jack,et al.  MRI‐Based Hippocampal Volume Measurements in Epilepsy , 1994, Epilepsia.

[30]  P. Landais,et al.  Apolipoprotein E‐ε4 allele doses in late‐onset Alzheimer's disease , 1994 .

[31]  S Lehéricy,et al.  Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease. , 1994, AJNR. American journal of neuroradiology.

[32]  A. Yamadori,et al.  MRI volumetry of medial temporal lobe structures in amnesia following herpes simplex encephalitis. , 1996, European neurology.

[33]  A D Roses,et al.  Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B. Hyman,et al.  Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions , 1993, Neuron.

[35]  S. Gauthier,et al.  Apolipoprotein E polymorphism and Alzheimer's disease , 1993, The Lancet.

[36]  C. Cuénod,et al.  Amygdala atrophy in Alzheimer's disease. An in vivo magnetic resonance imaging study. , 1993, Archives of neurology.

[37]  M. Pericak-Vance,et al.  Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[38]  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.

[39]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[40]  Gregory McCarthy,et al.  Quantitative magnetic resonance imaging in temporal lobe epilepsy: Relationship to neuropathology and neuropsychological function , 1992, Annals of neurology.

[41]  PhilipR. Wenham,et al.  Apolipoprotein E genotyping by one-stage PCR , 1991, The Lancet.

[42]  Robert A. Bornstein,et al.  The Wechsler Memory Scale—Revised , 1990 .

[43]  C. Jack,et al.  Anterior temporal lobes and hippocampal formations: normative volumetric measurements from MR images in young adults. , 1989, Radiology.

[44]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[45]  J. Coyle,et al.  Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. , 1982, Science.

[46]  J V Straumfjord,et al.  Analysis of brain weight. I. Adult brain weight in relation to sex, race, and age. , 1980, Archives of pathology & laboratory medicine.

[47]  A. Dekaban,et al.  Changes in brain weights during the span of human life: Relation of brain weights to body heights and body weights , 1978, Annals of neurology.

[48]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[49]  D. Wechsler.  Manual for the Wechsler Adult Intelligence Scale. , 1955 .

[50]  H. Soininen,et al.  SPECT and MRI analysis in Alzheimer's disease: relation to apolipoprotein E £4 allele , 2022 .