Senile dementia (SD) is a chronic and progressive disease that occurs in the elderly. Organic brain damage manifests as impaired mental function; behavioral disorders; and personality changes in cognition, memory, judgment, speech, emotion and thinking. SD encompasses a group of clinical syndromes and functional declines in daily life and social activities, which last for 4–6 months or more, and are mostly irreversible. Late-life dementia, in contrast to early-onset AD, can reflect damage to the brain by a wide range of vascular and nonvascular factors. to varying degrees, obesity, hypertension, diabetes, atrial fibrillation, high cholesterol, congestive heart failure, inflammatory conditions (such as lupus), obstructive sleep apnea (OSA), education, exercise, chronic stress, and depression can all alter brain architecture transiently or permanently at the cellular or macroscopic level.
Alzheimer’s disease (AD) is a progressive type of senile dementia affecting a large number of the elderly population. The pathological hallmarks of the disease are selective neuronal loss, numerous extracellular deposits termed senile plaques, and intraneuronal neurofibrillary tangles (NFTs) in the patient’s brain. The major component of senile plaques is a 39 to 43 amino acid peptide termed b-amyloid protein (AbP), which is a proteolytic product of a large precursor glycoprotein, the amyloid precursor protein (APP). Intracerebral application of AbP caused a decrease of choline acetyl transferase activity, impairment of long term potentiation, and the memory disorder. Furthermore, conformational changes of AbP have been linked to its neurotoxicity. AbP is a hydrophobic peptide and has the intrinsic property of forming aggregates with b-pleated sheet structures. A growing number of reports suggest that b-pleated sheet-AbP aggregates are neurotoxic. The neurotoxicity of AbP and its association with conformational changes of the peptide have been suggested to imply the etiological significance in the pathogenesis of AD.
Microglia, the resident innate immune cells in the brain, have been implicated as active contributors to neuron damage in neurodegenerative diseases, in which the overactivation and dysregulation of microglia might result in disastrous and progressive neurotoxic consequences. Pattern recognition receptors (PRRs) are tools used by microglia to identify neurotoxic stimuli and that stimulation of NADPH oxidase activity is the predominant mechanism through which microglia produce neurotoxic reactive oxygen species (ROS). Normal aging in the human brain is accompanied by increasing numbers of activated, interleukin 1β (IL-1β)-expressing microglia90 and enlarged phagocytic microglial subtypes. Several reports propose that the age-associated transformation of microglia is a reflection of a chronic, lifelong accumulation of minor insults leading to increased risk of neurodegenerative disease, such as Alzheimer’s disease.