Role of infection in the pathogenesis of Alzheimer's disease: implications for treatment.
While our understanding of the neuropathology of Alzheimer's disease continues to grow, its pathogenesis remains a subject of intense debate. Genetic mutations contribute to a minority of early-onset autosomal dominant cases, but most cases are of either late-onset familial or sporadic form. CNS infections, most notably herpes simplex virus type 1, Chlamydophila pneumoniae and several types of spirochetes, have been previously suggested as possible aetiological agents in the development of sporadic Alzheimer's disease but with little consistent evidence. However, peripheral infections may have a role to play in accelerating neurodegeneration in Alzheimer's disease by activating already primed microglial cells within the CNS. Potential pharmacological interventions could aim at modification of this peripheral inflammatory response through targeting various agents involved in this inflammatory pathway. However, benefit could also be gained clinically through the meticulous detection, treatment and prevention of infections in individuals either alone or in combination with anti-inflammatory therapy.
Holmes
Clive
C
University of Southampton, Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, UK. ch4@soton.ac.uk
Cotterell
Darren
D
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D000818:Animals; D002494:Central Nervous System Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D002690:Chlamydia Infections / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification; D006561:Herpes Simplex / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification; D006801:Humans; D013144:Spirochaetales / Q000302:isolation & purification; D013145:Spirochaetales Infections / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology