Introduction: Alzheimer’s disease (AD) is the most common cause of dementia globally and imposes a growing burden on healthcare systems.
Historical background: Alois Alzheimer reported the first case of AD in 1907, describing “particular changes in cortical cell clusters” on brain biopsy and attributing the patient’s behavioral changes to these lesions.
Pathogenesis: AD is a complex, multifactorial, neurodegenerative disease implicating the interactions of one’s genetic makeup, education, age, and environment. Currently the most accepted theory for the development of AD is the amyloid cascade hypothesis, which attributes clinical signs/symptoms to the overwhelming presence of amyloid beta (Ab) peptides, leading to increased deposition into amyloid plaques and the eventual result of neuronal damage.
Presentation: The most common presentation of those with AD involves an elderly individual with gradual decline in memory centered cognitive decline.
Testing: Though AD remains a clinical diagnosis, imaging such as fluorodeoxyglucose positron emission tomography (PET) and amyloid PET and biomarkers in cerebrospinal fluid (CSF) can be helpful in evaluating some patients.
Histology: The histology of AD is composed primarily of extracellular amyloid plaques consisting of misfolded Ab peptides and intracellular neurofibrillary tangles consisting of hyperphosphorylated tau. Eventually, these lead to gross anatomical findings of atrophy diffusely.
Treatment: Current pharmaceutical treatment available for AD include cholinesterase inhibitors as well as memantine. Other aims include increasing one’s cognitive reserve and providing a nutritional approach to prevent or slow the progression of disease.
Future Directions: Most therapeutics in development are intended to achieve disease modification by targeting amyloid plaques or neurofibrillary tangles of tau. There is increasing focus on identifying and prophylactically treating patients with preclinical AD and individuals with risk factors for cognitive decline.