Another new member of the team is Dr. Wes Ashford, senior scientist at the Stanford/VA NIH Alzheimer's Center, whose expertise is neuropsychological testing and the early incidence of Alzheimer's Disease.
Wes has a B.S. from UC-Berkeley, M.D. from UCLA-Geffen School of Medicine, and a Ph.D. in Neuroscience, also from UCLA.
Here is a summary of Dr. Ashford's AlzForum' presentation on genetic risk factors for Alzheimer's Disease:
ApoE's Strong Genetics :
J. Wesson (Wes) Ashford of the Stanford/VA Alzheimer's Center in Palo Alto, California, set the stage with a general review of the effect the ApoE genotype has on the epidemiology and onset of AD. He suggested that the onset of AD, like that of mortality and most age-related diseases, follows a descriptive, fundamental aging theory developed in 1825 by the British actuary Benjamin Gompertz. It holds that the death rate of a population doubles every set number of years. For humans aging without AD, this number has evolved to be 7.5 years for women and 8.2 for men. The specific Gompertz parameters underlying AD are not understood, but even so, it is clear that ApoE genotype changes this curve, Ashford said. Despite regional and ethnic variation in its prevalence, the ApoE4 allele overall is likely responsible for half of all nonfamilial AD cases in the US. First identified as a major AD risk factor by Allen Roses and colleagues, then at Duke University, in 1993 (Corder et al., 1993) , this allele occurs in 22 percent of the population, but in 60 percent of AD cases, whereas the E2 and E3 alleles together occur in 78 percent of the population, but only 40 percent of AD cases. ApoE exerts its main effect by influencing when people get AD, Ashford said. In a clinic population, the E4/4 genotype reduces the mean age of onset to 68 from 74 in E3/3 carriers.
Environmental factors and nonspecific genes also play a role in determining AD risk and may, in fact, have a relatively greater effect in very old age (see also Silverman et al., 2003). Ashford suggested that the E2 and E3 alleles, which evolved from the ancestral E4, better support the remodeling of dendrites and minimize neuronal stress over time (see also Live Discussion). E4 also has an inferior ability to handle (excess) animal fat, and its exposure to contemporary environmental conditions with its Western diet and longer lifespans could have made it a susceptibility allele for coronary heart disease and AD (see Corbo and Scacchi, 1999). Allen Roses of GlaxoSmithKline in Research Triangle Park recalled earlier attempts at studying AD in populations that have high E4/4 rates, including African pygmies, Australian aborigines and native Brazilian tribes. The study was difficult, in part because these groups tended to die too young to develop AD in significant numbers, but the few who were available for study had massive neurodegeneration.
List of publications from PUBMED search
ARTICLES REFERENCED ON "PUBMED" to Ashford JW
- some PDF files available (5/22/2004) (52 references)
and 2 papers in press and 1 book chapter
Raber J, Huang, Y, Ashford JW, ApoE genotype accounts for the vast majority of AD risk and AD neuropathology.
Neurobiology of Aging 2004. PDF
Ashford JW. APOE genotype effects on Alzheime's disease onset and epidemiology.
Journal of Molecular Neuroscience 23:155-163, 2004. PDF
Mendiondo MS, Ashford JW, Kryscio RJ, Schmitt FA. Designing a brief Alzheimer screen (BAS).
J Alzheimers Dis. 2003 Dec 5:391-398. PDF
Teter B, Ashford JW.
Neuroplasticity in Alzheimer's disease.
J Neurosci Res. 2002 Nov 1;70(3):402-37. PDF
Ashford JW, Mortimer JA.
Non-familial Alzheimer's disease is mainly due to genetic factors.
J Alzheimers Dis. 2002 Jun;4(3):169-77. PDF
ApoE4: is it the absence of good or the presence of bad?
J Alzheimers Dis. 2002 Jun;4(3):141-3. No abstract available. PDF
Ashford JW, Schmitt FA.
Modeling the time-course of Alzheimer dementia.
Curr Psychiatry Rep. 2001 Feb;3(1):20-8. PDF
Schmitt FA, Davis DG, Wekstein DR, Smith CD, Ashford JW, Markesbery WR. Preclinical" AD revisited: neuropathology of cognitively normal older adults.
Neurology. 2000 Aug 8;55(3):370-6. PDF
Mendiondo MS, Ashford JW, Kryscio RJ, Schmitt FA. Modelling mini mental state examination changes in Alzheimer's disease.
Stat Med. 2000 Jun 15-30;19(11-12):1607-16. PDF
Ashford JW, Shih WJ, Coupal J, Shetty R, Schneider A, Cool C, Aleem A, Kiefer VH, Mendiondo MS, Schmitt FA. Single SPECT measures of cerebral cortical perfusion reflect time-index estimation of dementia severity in Alzheimer's disease.
J Nucl Med. 2000 Jan;41(1):57-64.
Shih WJ, Ashford JW, Coupal JJ, Ryo YU, Stipp V V, Magoun SL, Gross K. Consecutive brain SPECT surface three-dimensional displays show progression of cerebral cortical abnormalities in Alzheimer's disease
Clin Nucl Med. 1999 Oct;24(10):773-7.
Shih WJ, Wilson D, Stipp V, Ashford JW.Heterogenous uptake on brain SPECT.
Semin Nucl Med. 1999 Jan;29(1):85-8. No abstract available.
Ashford JW, Mattson M, Kumar V. Neurobiological systems disrupted by Alzheimer's disease and molecular biological theories of vulnerability.
In Advances in the Diagnosis and Treatment of Alzheimer's Disease. Kumar V. Eisdorfer C. eds, Springer Publishing Company, New York, 1998:85-8. PDF
Ashford JW, Soultanian NS, Zhang SX, Geddes JW. Neuropil threads are collinear with MAP2 immunostaining in neuronal dendrites of Alzheimer brain.
J Neuropathol Exp Neurol. 1998 Oct;57(10):972-8.
Piecoro LT, Wermeling DP, Schmitt FA, Ashford JW. Seizures in patients receiving concomitant antimuscarinics and acetylcholinesterase inhibitor.
Pharmacotherapy. 1998 Sep-Oct;18(5):1129-32.
Pettigrew LC, Bieber F, Lettieri J, Wermeling DP, Schmitt FA, Tikhtman AJ, Ashford JW, Smith CD, Wekstein DR, Markesbery WR, Orazem J, Ruzicka BB, Mas J, Gulanski B. Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with Alzheimer's disease.
J Clin Pharmacol. 1998 Mar;38(3):236-45.
Shih WJ, Davis DG, Stipp V, Ashford W, Magoun S. Bilateral perfusion defect/hypoperfusion in temporal and parietal regions on brain SPECT.
Semin Nucl Med. 1998 Apr;28(2):192-3. No abstract available.
Schmitt FA, Ashford W, Ernesto C, Saxton J, Schneider LS, Clark CM, Ferris SH, Mackell JA, Schafer K, Thal LJ. The severe impairment battery: concurrent validity and the assessment of longitudinal change in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.
Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S51-6.
Geddes JW, Tekirian TL, Soultanian NS, Ashford JW, Davis DG, Markesbery WR. Comparison of neuropathologic criteria for the diagnosis of Alzheimer's disease.
Neurobiol Aging. 1997 Jul-Aug;18(4 Suppl):S99-105.
Butler SM, Ashford JW, Snowdon DA. Age, education, and changes in the Mini-Mental State Exam scores of older women: findings from the Nun Study.
J Am Geriatr Soc. 1996 Jun;44(6):675-81.
Ashford JW, Shan M, Butler S, Rajasekar A, Schmitt FA. Temporal quantification of Alzheimer's disease severity: 'time index' model.
Dementia. 1995 Sep-Oct;6(5):269-80.
Semla TP, Cohen D, Freels S, Paveza GJ, Ashford JW, Gorelick P, Luchins D, Eisdorfer C. Psychotropic drug use in relation to psychiatric symptoms in community-living persons with Alzheimer's disease.
Pharmacotherapy. 1995 Jul-Aug;15(4):495-501.
Smith CJ, Lippiello PM, Ashford JW. Smoking, Alzheimer's disease, and confounding with genes.
Lancet. 1995 Apr 22;345(8956):1054. No abstract available.
Mark RJ, Ashford JW, Goodman Y, Mattson MP. Anticonvulsants attenuate amyloid beta-peptide neurotoxicity, Ca2+ deregulation, and cytoskeletal pathology.
Neurobiol Aging. 1995 Mar-Apr;16(2):187-98.
Cohen D, Eisdorfer C, Gorelick P, Paveza G, Luchins DJ, Freels S, Ashford JW, Semla T, Levy P, Hirschman R. Psychopathology associated with Alzheimer's disease and related disorders.
J Gerontol. 1993 Nov;48(6):M255-60.
Coburn KL, Ashford JW, Moreno MA. Delayed late component of visual global field power in probable Alzheimer's disease.
J Geriatr Psychiatry Neurol. 1993 Apr-Jun;6(2):72-7.
Semla TP, Cohen D, Paveza G, Eisdorfer C, Gorelick P, Luchins D, Hirschman R, Freels S, Levy P, Ashford JW, et al. Drug use patterns of persons with Alzheimer's disease and related disorders living in the community.
J Am Geriatr Soc. 1993 Apr;41(4):408-13.
Cohen D, Eisdorfer C, Gorelick P, Luchins D, Freels S, Semla T, Paveza G, Shaw H, Ashford JW. Sex differences in the psychiatric manifestations of Alzheimer's disease.
J Am Geriatr Soc. 1993 Mar;41(3):229-32.
Hargrave R, Ashford JW. Phenelzine treatment of depression in Parkinson's disease.
Am J Psychiatry. 1992 Dec;149(12):1751-2. No abstract available.
Freels S, Cohen D, Eisdorfer C, Paveza G, Gorelick P, Luchins DJ, Hirschman R, Ashford JW, Levy P, Semla T, et al. Functional status and clinical findings in patients with Alzheimer's disease.
J Gerontol. 1992 Nov;47(6):M177-82.
Brewer GJ, Ashford JW. Human serum stimulates Alzheimer markers in cultured hippocampal neurons.
J Neurosci Res. 1992 Nov;33(3):355-69.
Paveza GJ, Cohen D, Eisdorfer C, Freels S, Semla T, Ashford JW, Gorelick P, Hirschman R, Luchins D, Levy P. Severe family violence and Alzheimer's disease: prevalence and risk factors.
Gerontologist. 1992 Aug;32(4):493-7.
Luchins DJ, Cohen D, Hanrahan P, Eisdorfer C, Paveza G, Ashford JW, Gorelick P, Hirschman R, Freels S, Levy P, et al. Are there clinical differences between familial and nonfamilial Alzheimer's disease?
Am J Psychiatry. 1992 Aug;149(8):1023-7.
Eisdorfer C, Cohen D, Paveza GJ, Ashford JW, Luchins DJ, Gorelick PB, Hirschman RS, Freels SA, Levy PS, Semla TP, et al. An empirical evaluation of the Global Deterioration Scale for staging Alzheimer's disease.
Am J Psychiatry. 1992 Feb;149(2):190-4.
Ashford JW, Kumar V, Barringer M, Becker M, Bice J, Ryan N, Vicari S. Assessing Alzheimer severity with a global clinical scale.
Int Psychogeriatr. 1992 Summer;4(1):55-74.
Coburn KL, Ashford JW, Moreno MA. Visual evoked potentials in dementia: selective delay of flash P2 in probable Alzheimer's disease.
J Neuropsychiatry Clin Neurosci. 1991 Fall;3(4):431-5.
Cohen D, Paveza G, Levy PS, Ashford JW, Brody JA, Eisdorfer C, Gorelick P, Hirschman R, Luchins D, Trozzolo T, et al. An Alzheimer's disease patient registry: the Prototype Alzheimer Collaborative Team (PACT).
Aging (Milano). 1990 Sep;2(3):312-6. No abstract available.
Coburn KL, Ashford JW, Fuster JM. Visual response latencies in temporal lobe structures as a function of stimulus information load.
Behav Neurosci. 1990 Feb;104(1):62-73.
Ashford JW, Kolm P, Colliver JA, Bekian C, Hsu LN. Alzheimer patient evaluation and the mini-mental state: item characteristic curve analysis.
J Gerontol. 1989 Sep;44(5):P139-46.
Small GW, Kuhl DE, Riege WH, Fujikawa DG, Ashford JW, Metter EJ, Mazziotta JC. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset.
Arch Gen Psychiatry. 1989 Jun;46(6):527-32.
Ashford JW, Sherman KA, Kumar V. Advances in Alzheimer therapy: cholinesterase inhibitors.
Neurobiol Aging. 1989 Jan-Feb;10(1):99-105.
Parks RW, Crockett DJ, Tuokko H, Beattie BL, Ashford JW, Coburn KL, Zec RF, Becker RE, McGeer PL, McGeer EG. Neuropsychological "systems efficiency" and positron emission tomography.
J Neuropsychiatry Clin Neurosci. 1989 Summer;1(3):269-82. Review.
Small GW, Kuhl DE, Fujikawa DG, Ashford JW. Clinical characterization of Alzheimer's disease: reliability of 'age at onset' and a new descriptor, 'age at shift'.
J Geriatr Psychiatry Neurol. 1988 Oct-Dec;1(4):207-11.
Kumar V, Smith RC, Sherman KA, Ashford W, Murphy J, Giacobini E, Colliver J. Cortisol responses to cholinergic drugs in Alzheimer's disease.
Int J Clin Pharmacol Ther Toxicol. 1988 Oct;26(10):471-6.
Ashford JW, Fuster JM. Occipital and inferotemporal responses to visual signals in the monkey.
Exp Neurol. 1985 Nov;90(2):444-66.
Ashford JW, Coburn KL, Fuster JM. The elgiloy microelectrode: fabrication techniques and characteristics.
J Neurosci Methods. 1985 Sep;14(4):247-52.
Ashford JW, Jarvik L. Alzheimer's disease: does neuron plasticity predispose to axonal neurofibrillary degeneration?
N Engl J Med. 1985 Aug 8;313(6):388-9. No abstract available.
Fuster JM, Willey TJ, Riley DM, Ashford JW. Effects of ethanol on visual evoked responses in monkeys performing a memory task.
Electroencephalogr Clin Neurophysiol. 1982 Jun;53(6):621-33.
Ashford JW, Soldinger S, Schaeffer J, Cochran L, Jarvik LF. Physostigmine and its effect on six patients with dementia.
Am J Psychiatry. 1981 Jun;138(6):829-30. No abstract available.
Ashford JW, Schulz C, Walsh GO. Violent automatism in a partial complex seizure. Report of a case. Arch Neurol. 1980 Feb;37(2):120-2.
Ashford JW, Ford CV. Use of MAO inhibitors in elderly patients.
Am J Psychiatry. 1979 Nov;136(11):1466-7. No abstract available.