Familial Alzheimer's disease (FAD) or early onset familial Alzheimer's disease (EOFAD) is an uncommon form of Alzheimer's disease that usually strikes earlier in life, defined as before the age of 65 (usually between 50 and 65 years of age, but can be as early as 15) and is inherited in an autosomal dominant fashion, identified by genetics and other characteristics such as the age of onset. It accounts for approximately half the cases of early-onset Alzheimer's disease. Familial AD requires the patient to have at least one first degree relative with a history of AD. Non-familial cases of AD are referred to as "sporadic" AD, where genetic risk factors are minor or unclear.[citation needed]

While early-onset familial AD is estimated to account for only 3.5% of total Alzheimer's disease,[2] it has presented a useful model in studying various aspects of the disorder. Currently, the early-onset familial AD gene mutations guide the vast majority of animal model based therapeutic discovery and development for AD.[citation needed]

Alzheimer's disease (AD) is the most common cause of dementia and usually occurs in old age. It is invariably fatal, generally within ten years of the first signs. Early signs of AD include unusual memory loss, particularly in remembering recent events and the names of people and things, logopenic primary progressive aphasia. As the disease progresses the patient exhibits more serious problems, becoming subject to mood swings and unable to perform complex activities such as driving. In the latter stages they forget how to do simple things such as brushing their hair and then require full-time care.

Histologically, familial AD is practically indistinguishable from other forms of the disease. Deposits of amyloid can be seen in sections of brain tissue. This amyloid protein forms plaques and neurofibrillary tangles that progress through the brain. Very rarely the plaque may be unique, or uncharacteristic of AD; this can happen when there is a mutation in one of the genes that creates a functional, but malformed, protein instead of the ineffective gene products that usually result from mutations.[citation needed]

The underlying neurobiology of this disease is just recently starting to be understood. Researchers have been working on mapping the inflammation pathways associated with the development, progression, and degenerative properties of Alzheimer's disease. The major molecules involved in these pathways include: glial cells (specifically astrocytes and microglia), beta-amyloid, and pro-inflammatory compounds.

Beta-amyloid is a small piece of a larger protein called the amyloid precursor protein (APP). Once APP is activated it is cut into smaller sections of other proteins. One of the fragments produced in this cutting process is β-amyloid. β-amyloid is “stickier” than any other fragment produced from cut-up APP and due to this property it starts an accumulation process in the brain. The accumulation is due to various genetic and biochemical abnormalities. Eventually, the fragments form oligomers, then fibrils, beta-sheets, and finally plaques. The presence of β-amyloid plaques in the brain causes the body to recruit and activate microglial cells and astrocytes. This is typically a beneficial response; however not with Alzheimer's because β-amyloid plaques stimulate the glial cells to release oxygen free radicals (this pathway is not yet clear). Free radicals are typically effective against abnormal cells, but there is no way for the free radicals to differentiate between normal and abnormal cells. The free radicals destroy β-amyloid plaques but also destroy the surrounding healthy tissue. As more tissue dies, the glial cells release chemokines and cytokines (pro-inflammatory compounds). These compounds recruit more glial cells, which means more free radicals. This uncontrolled glial response and inflammatory storm directly contributes to the neurodegenerative progression of Alzheimer's.

Early Onset Alzheimer's