15.7: Alzheimer’s Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.

The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau proteins in the cerebrospinal fluid, are increasingly incorporated into the diagnostic criteria. Imaging biomarkers, such as hippocampal atrophy and cortical hypometabolism, also play a crucial role in confirming the diagnosis.

In some cases, gene mutations in APP, PSEN1, and PSEN2 genes can trigger early-onset AD with autosomal dominance. The pathophysiology of AD is marked by two key hallmarks: amyloid plaques, which are extracellular accumulations of Aβ, and neurofibrillary tangles composed of tau protein. These pathological changes induce neuronal dysfunction and death through synaptic impairment, excitotoxicity, oxidative stress, and neuroinflammation.

Regarding neurochemistry, the most significant disturbance in AD is a deficiency in acetylcholine (ACh), which stems from the atrophy and degeneration of subcortical cholinergic neurons. Current treatments mainly aim to alleviate symptoms, with cholinesterase inhibitors and memantine (Namenda) as the primary drugs. Behavioral and psychiatric symptoms common in AD can be managed with these drugs, serotonergic antidepressants, or atypical antipsychotics. Ongoing research explores anti-amyloid antibodies and other drugs that target amyloid beta and tau protein to modify the course of AD.

Alzheimer's disease, or AD, is a neurodegenerative disorder primarily affecting older adults, causing impaired memory and cognitive decline through three stages: preclinical, mild cognitive impairment, and dementia.

Its pathophysiology involves Aβ amyloid plaques and tau protein neurofibrillary tangles, resulting in cholinergic neuron loss.

Neurochemically, AD exhibits reduced neurotransmitter levels of acetylcholine, serotonin, and norepinephrine.

Its clinical diagnosis includes medical evaluation, brain imaging, neuropsychological assessment, and cerebrospinal fluid analysis.

Specific biomarkers like Aβ and tau protein changes in cerebrospinal fluid, and hippocampal atrophy, and cortical hypometabolism in imaging,  confirms AD.

Certain gene mutations, such as APP, PSEN1, and PSEN2, can trigger early-onset AD with autosomal dominance.

Biochemical changes in AD include inflammation, oxidative stress, and mitochondrial dysfunction.

Current treatments prioritize symptom relief and disease progression deceleration. For instance, cholinesterase inhibitors are used to manage behavioral symptoms.