Role of Folate and Homocysteine in Alzheimer's Disease Examined

In a special issue of the Journal of Alzheimer's Disease published this month, ten contributions from worldwide experts in the field examine possible linkages between folate and homocysteine and Alzheimer's disease.

In the lead article Guest Editor Thomas Shea, Professor and Director of the Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts Lowell, suggests “Alzheimer’s disease has a multifactoral etiology, encompassing genetic and nutritional risk factors, and no single risk factor can account for all cases.…A genetic predisposition may remain latent pending an age-related critical decline in nutrition. This has confounded the linkage of nutrition to Alzheimer’s disease, since contributing nutritional deficiencies may remain undetected, and, even if considered, may not receive sufficient attention if they are benign in isolation.”

Andrew McCaddon from the Wales College of Medicine contributes some historical perspective on homocysteine and folate levels and the development of dementia, including some discussion of the potential for reversing such declines.

Aron M. Troen and colleagues from Tufts University write of their studies of mice fed diets to create excess homocysteine levels and then tested for cognitive functions. Sudha Seshadri discusses whether elevated homocysteine levels is a risk factor for dementia or merely a risk marker for some underlying process. Amy Chan and Thomas B. Shea then examine the connection between dietary deficiencies of folate and Vitamin E and the development of neurofibrillary tangles of tau protein, a hallmark of Alzheimer's disease.

Moving on to possible therapies, Sigfrido Scarpa and colleagues at the University of Rome investigated S-adenosylmethionine (SAM) metabolism in cell cultures, which might be used to interfere with amyloid-ß overproduction, another characteristic of AD. In a second contribution from that institution, Rosaria A. Cavallaro and co-workers looked at whether SAM administration influences gene expression in the brain.

Flaubert Tchantchou of the University of Maryland School of Pharmacy discusses the various metabolic processes involved in homocysteine regulation and the various consequences of folate deficiency.

Folate is one of the B vitamins. Martha Clare Morris and colleagues at the Rush University Medical Center expand on the possible role of all of the B vitamins in cognitive decline and comment on the potential benefits and harms of vitamin supplementation. In another contribution, Morris and coworkers report on a prospective cohort study of 1041 patients where dietary folate, B-12 and B-6 levels were not associated with the development of Alzheimer's disease.

SPECIAL ISSUE: FOLATE AND HOMOCYSTEINE IN ALZHEIMERS DISEASE
Guest Editor: Thomas B. Shea, University of Massachusetts Lowell
Journal of Alzheimer's Disease, Volume 9, Issue 4 (September 2006)
TABLE OF CONTENTS
Folate, the methionine cycle, and Alzheimer's disease
Thomas B. Shea
Homocysteine and cognition – A historical perspective
Andrew McCaddon
The cognitive impact of nutritional homocysteinemia in Apolipoprotein-E deficient mice

Aron M. Troen, Barbara Shukitt-Hale, Wei-Hsun Chao, Bina Albuquerque, Donald E. Smith, Jacob Selhub, Jacob Rosenberg

Elevated plasma homocysteine levels: Risk factor or risk marker for the development of dementia and Alzheimer's disease?

Sudha Seshadri

Dietary and genetically-induced oxidative stress alter tau phosphorylation: Influence of folate and apolipoprotein E deficiency

Amy Chan and Thomas B. Shea

Gene silencing through methylation: An epigenetic intervention on Alzheimer disease

Sigfrido Scarpa, Rosaria A. Cavallaro, Fabrizio D'Anselmi, Andrea Fuso

The effect of S-adenosylmethionine on CNS gene expression studied by cDNA microarray analysis

Rosaria A. Cavallaro, Andrea Fuso, Fabrizio D'Anselmi, Laura Seminara, Sigfrido Scarpa

Homocysteine metabolism and various consequences of folate deficiency
Flaubert Tchantchou
Thoughts on B-vitamins and dementia
Martha Clare Morris, Julie A. Schneider, Christine C. Tangney
Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer's disease

Martha Clare Morris, Denis A. Evans, Julie A. Schneider, Christine C. Tangney, Julia L. Bienias, Neelum T. Aggarwal

Selected Abstracts From the “Wellness For Persons With Dementia” Symposium
Nancy B. Emerson Lombardo
Discussion
Alzheimer Research Forum Live Discussion: Lost in Translation? Charting the Course in Preclinical Therapeutic Development