Discoveries in AD Information & Diagnosis
Familial AD and Herpes Simplex Virus Type 1. Dr. Isamu Mori and colleagues from Aichi Medical University School of Medicine (Aichi, Japan) used nested PCR to study brain tissue from individuals with familial AD and individuals with sporadic AD. Herpes Simplex Virus Type 1 (HSV-1) was detected in all cases. In a related study of the brains of the individuals with familial AD, high-sensitivity immunohistochemistry revealed HSV-1antigens in the cytoplasm of cortical neurons, providing the first evidence of reactivation of HSV-1 associated with beta-amyloid deposition. The possible involvement of HSV-1 in conjunction with genetic factors suggests that infection may contribute to the etiology of familial AD.
Diabetics at increased risk of developing AD. In a longitudinal cohort study involving 824 Catholic nuns, priests, and brothers age 55 and over, Dr. Zoe Arvanitakis and colleagues from the Rush Alzheimer's Disease Center, the Department of Neurological Sciences, Rush University Medical Center (Chicago, IL, USA) determined that diabetes mellitus was present in 127 (15.4%) of the participants. During a mean of 5.5 years of observation, 151 persons developed AD. In a proportional hazards model adjusted for age, sex, and educational level, those with diabetes mellitus had a 65% increase in the risk of developing AD compared with those without diabetes mellitus (hazard ratio,1.65; 95% confidence interval, 1.10-2.47).
In random effects models, diabetes mellitus was associated with lower levels of global cognition, episodic memory, semantic memory, working memory, and visuospatial ability at baseline. Diabetes mellitus was associated with a 44% greater rate of decline in perceptual speed =.02), but not in other cognitive systems. The researchers conclude that: "Diabetes mellitus may be associated with an increased risk of developing AD and may affect cognitive systems differentially."
Low TSH as risk factor for AD. Dr. Van Osch and colleagues from the University of Oxford and Radcliffe Infirmary (United Kingdom) found that AD patients had significantly lower levels of thyroid stimulating hormone (TSH) than control subjects. Lower TSH was associated with a 2.36-fold greater risk of AD (95% CI=1.19 to 4.67), independent of other risk factors and confounding variables.
Antibody marker for AD found. Dr. Mruthinti and colleagues from the Alzheimer's Research Center, Department of Pharmacology and Toxicology, Medical College of Georgia (Augusta, GA USA) found that leukocytes in AD patients contain four-times the levels of markers for amyloid-b peptide and receptor for advanced glycation end products (RAGE) than in non-AD subjects.
The research could lead to a way to identify people at risk for AD and enable the establishment of an early diagnosis.
Androgen loss may lead to AD. Dr. Christian Pike and team from the University of Southern California (USA) reported that "age-related testosterone depletion is one of the important changes that promote Alzheimer's disease in men." Furthermore, Dr. Pike stated that "testosterone has at least two critical brain functions relevant to AD. It protects neurons from injury, and it reduces levels of beta-amyloid. The loss of testosterone with advancing age creates a more hostile neural environment." He and his colleagues also suggest that the brain is like any other tissue that experiences the effects of testosterone loss with age, and that increased vulnerability to AD should be considered a component of the clinical syndrome known as androgen deficiency in aging males (ADAM).
Low hemoglobin levels as risk factor for AD. Dr. Pandav and colleagues from the University of Pittsburgh Medical School (Pennsylvania, USA) evaluated hemoglobin levels in persons age 55 and over living in India, one of the world's fastest aging countries and one in which anemia is a common medical problem. Low hemoglobin was found to correlate to AD, and the researchers suggest further investigation to establish whether or not hemoglobin is a modifiable risk factor for the disease.
Discoveries in AD Prevention
Combination of vitamins E and C reduce AD risk. In a cross-sectional, prospective study involving 104 cases of AD, Dr. Zandi and colleagues from the Bloomberg School of Public Health, The Johns Hopkins University (Baltimore, MD USA) administered various combinations of vitamin E (400 to 800IU), vitamin C (500 to 1,000 mg), and a multivitamin. The team found that vitamin E and C intake was associated with a 22% reduction in AD incidence at baseline, and a 36% reduction in AD prevalence at follow-up. When taken alone, neither the multivitamins nor vitamins E or C produced a protective effect on AD risk. However, taking vitamin E with a multivitamin containing vitamin C trended toward a lower AD risk. The researchers presume that when water-soluble vitamin C is oxidized, it activates the fat-soluble vitamin E, making vitamin E better able to scour free radicals and be oxidized itself.
Low vitamin B12 is associated with poorer memory in older people with familial AD. A large-scale study by Dr. David Bunce from Goldsmith's College, University of London (United Kingdom) and colleagues from Stockholm, Sweden revealed that among healthy people over the age of 75 who have the APOe-4 gene and are thus at higher risk for AD, low levels of vitamin B12 are associated with significantly worse performance on memory tests. Conversely, carriers of the APOe-4 allele with normal B12 levels scored higher on verbal memory tests. The researchers suggest that: "APOe-4 carriers may derive relatively greater cognitive benefits from B12 and folate supplements."
Niacin may protect against AD. Dr. Martha Morris from the Rush Institute for Healthy Aging (Chicago, IL USA) and colleagues studied 815 subjects of whom, after four years, 131 developed AD. A high level of total niacin intake seemed to protect against AD and cognitive decline. Compared with the lowest intake, the highest levels of niacin intake "was linked to an 80% reduction in risk," remarked Dr. Morris. The findings may prompt changes to current dietary guidelines for the elderly.
Discoveries in AD Treatment
RNA interference silences alleles responsible for AD. Dr. Miller and colleagues from the University of Iowa (Iowa City, IA USA) designed a method to produce small interfering RNA (siRNA) to counteract the tau mutation (V337M) and AAP mutation (APPsw) responsible for the proteins that characterize AD. The allelespecific RNA duplexes produced by this method then served as templates with which the researchers constructed short hairpin RNA (shRNA) plasmids that successfully silenced mutant tau and APP alleles.
Gene therapy surgery helps AD. Dr. Mark Tuszynski and team from the University of California/San Diego (USA) increased the brain activity of eight men and women with early-stage AD by implanting genetically engineered cells.
Dr. Tuszynski's team took skin samplesfrom each subject, and genetically modified them to make the cells produce extra nerve growth factor, a protein that prevents cell death and stimulates cell function. The cells were then implanted respectively into each patient from whom they originated. In all eight participants,the gene therapy surgery resulted with increased brain activity and the progression of AD slowed over time. Dr. Tuszynski is hopeful that long-term follow-up will determine the viability of proceeding to larger, controlled trials of gene therapy surgery as a treatment for AD.
Two new AD drugs in final stages of trials. Two experimental AD drugs have the potential to prevent or halt the progress of AD. Alzhemed, made by Montreal, Canada-based Neurochem Inc., is a pill currently in Phase III trials. In a study at Georgetown University Medical Center (Washington, DC USA),58 subjects with AD took Alzhemed for a total of 24 months, at which time a significant drop in the level of betaamyloid was found. Among patients who began the trial with mild AD, there was no further cognitive decline after 12 months of taking the drug.
Eli Lilly & Co.'s LY450139 seeks to prevent beta-amyloid accumulation. A trial of 37 healthy adults over age 45 found blood levels of beta-amyloid were reduced after they took the experimental drug, which is designed to interfere with the secretases that generate beta-amyloid. The degree of reduction in beta-amyloid accumulation was dose-dependent on the amount of LY450139 administered.
Concluding Remarks
While Alzheimer's Disease was first discovered at the start of the 20th century in 1906, little was known about the disorder until the latter-half of that century, with a wealth of knowledge amassing in the past decade alone.
Today, it is possible to diagnose AD at an early preclinical stage. We now have a handful of medications that mitigate symptoms, and there are a host of promising new treatments in the pipeline. While there presently is no cure for the disease, as this review demonstrates, medical and scientific knowledge are advancing so rapidly that, in a few years from now, there is a good chance that AD may be a thing of the past.
Given that, in the absence of disease, the human brain often can function well into the tenth decade of life, a world free of Alzheimer's will rid society of the extraordinary economic burden of the disease, which currently costs $100 billion annually in the United States alone.
Perhaps more importantly, the devastating emotional and physical stress the disease imposes on families, friends, and caregivers as they cope with the physical and mental changes in their loved ones will at last be ifted.
