Alzheimer's Disease is the most common form of dementia in North America. It is a degenerative brain disease that is estimated to affect about one in 85 people. Worldwide, more than 25 million people are afflicted with Alzheimer's Disease.

A specific protein, Apolipoprotein E, has been strongly linked to Alzheimer's Disease. There are four different variations of this protein; which are referred to as E1, E2, E3 and E4. While most people's bodies produce the E3 variant, people who have the E4 variant are significantly more likely to develop non-familial Alzheimer's Disease. The protein apolipoprotein E4 (apoE4) is the only genetic risk factor that has been consistently found associated with the late-onset form of AD.

We test for the genes that cause these variations.

Background

Alzheimer's disease, the most common cause of dementia, is an acquired cognitive and behavioral impairment of sufficient severity that markedly interferes with social and occupational functioning. Alzheimer's disease is a major public health problem from the economic perspective. In the United States, the cost of caring for patients with dementia was $144 billion per year in 2009.

Causes

Even though the cause of Alzheimer disease is unknown, several researches now believe that many converging risk factors, lead to Alzheimer pathology and dementia. These risk factors include advancing age, APOE4 genotype, obesity, insulin resistance, vascular factors, dyslipidemia, hypertension, and inflammatory markers trigger a pathophysiologic cascade.

Majority of Alzheimer's cases are sporadic and only 7% are attributed to being familial in their nature.Scientists were able to detemine that mutations in 3 genes lead to Alzheimer's disease. These genes (amyloid precursor protein, presenilin I, and presenilin II) all result in a relative excess in the production of the stickier 42-amino acid form of the beta-amyloid peptide over the less sticky 40-amino acid form.

This beta-pleated peptide is thought to have neurotoxic properties and to lead to a cascade of events resulting in neuronal death, synapse loss, and the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) among other lesions, however this process is not fully understood yet. Some mutations accounting for less than half of all cases of early-onset Alzheimer's disease have been discovered. However, other than the ApoE4 genotype, no polymorphisms in other genes have been consistently found to be associated with late-onset Alzheimer disease.

Considerable attention has been devoted to determining the composition of NFTs and SPs to find clues about the nature of molecular pathogenesis and biochemistry of Alzheimer's disease. SPs have been known to include a starch-like (or amyloid) substance, usually in the center of these lesions, which is surrounded by a halo or layer of degenerating (dystrophic) neurites and reactive glia (both astrocytes and microglia).

One of the most important advances in recent decades has been the chemical characterization of this amyloid protein, the sequencing of its amino acid chain, and the cloning of the gene encoding its precursor protein (on chromosome 21). These advances have provided a wealth of information about the mechanisms underlying amyloid deposition in the brain, including information about the familial forms of Alzheimer’s disease. Although the amyloid cascade hypothesis has gathered the most research dollars, other interesting hypotheses have been proposed, including the mitochondrial cascade hypothesis.

Attention has also been devoted to the mechanisms leading to the development of NFTs, the main constituent of which is the microtubule-associated protein tau that is hyperphosphorylated and that accumulates in the perikarya of large and medium pyramidal neurons. Somewhat surprisingly, mutations of the tau gene result not in Alzheimer disease but in some familial cases of frontotemporal dementia.

Symptoms

The earliest evidence of Alzheimer's disease is the onset of chronic, insidious memory loss that is slowly progressive over several years. This loss may be associated with slowly progressive behavioral changes. Patients with mild Alzheimer disease usually have somewhat less obvious executive, language, and/or visuospatial dysfunction. In atypical presentations, dysfunction in cognitive domains other than memory may be most apparent. In later stages, many patients develop extrapyramidal dysfunction.

Initial mental status testing should include evaluation of attention and concentration, recent and remote memory, language, praxis, executive function, and visuospatial function. Brief standardized examinations such as the Mini-Mental Status Examination are less sensitive and specific than longer batteries specifically tailored to individual patients. Nonetheless, screening exams have a role, particularly as a baseline.