Alzheimer Disease l: Introduction

Alzheimer disease is characterized by extracellular neuritic plaques and intracellular neurofibrillary tangles that accumulate in the brain. These abnormal protein deposits lead to gradual neuronal loss, which causes cognitive decline and behavioral changes. Over time, this neurodegeneration results in loss of functional independence in affected individuals.

Age is the strongest risk factor for Alzheimer disease, with prevalence roughly doubling every five years after age 65. This exponential increase makes older adults significantly more susceptible to the condition. The disease remains rare in younger populations but becomes increasingly common with advancing age.

Mutations in the APP, PSEN1, and PSEN2 genes are associated with early-onset familial Alzheimer disease. Additionally, individuals with Down syndrome develop early Alzheimer-related changes due to an extra copy of the APP gene. These genetic factors account for inherited forms of the disease that appear before age 65.

Modifiable risk factors include hypertension, stroke, obesity, type 2 diabetes, head trauma, and smoking. These factors contribute to vascular injury, inflammation, and oxidative stress that can damage neurons over time. Type 2 diabetes particularly accelerates neurodegeneration through inflammation and vascular damage.

The disease typically begins with short-term memory loss and difficulty learning new information. It progresses to language deficits, disorientation, and psychiatric symptoms including depression. In advanced stages, patients experience failure to recognize familiar people and motor changes such as slowed movement and gait disturbances.

The APOE ε4 allele increases the risk of late-onset Alzheimer disease, distinguishing it from early-onset genetic mutations. This genetic variant is a significant risk factor for the more common form of the disease that develops after age 65. Individuals carrying this allele have elevated susceptibility compared to those without it.

Alzheimer disease is the most common cause of dementia in older adults and is characterized by specific pathological hallmarks: extracellular neuritic plaques and intracellular neurofibrillary tangles. Understanding these distinctive features helps differentiate it from other neurodegenerative disorders and guides clinical diagnosis and management strategies.