FREE-RADICAL THEORY OF AGING - ALZHEIMERS-DISEASE PATHOGENESIS

Senile dementia of the Alzheimer's type (SDAT) is the major cause of d ementia. SDAT cases can be categorized into two groups: 1) late onset, after about age 60, 90-95 percent of cases; largely non-familial, i.e ., sporadic, 2) early onset, before about age 60; 5-10 percent of case s, most - ii not all - are familial. It is a systemic disorder whose m ajor manifestations are in the brain. The brain lesions in both early and late-onset SDAT are the same as those seen in smaller numbers in n ormal older individuals. It is hypothesized that SDAT is caused by inc reased free radical reaction levels in brain neurons that advance in t ime patterns of neuronal dysfunction and cell loss. Measures to this e nd include: I)mutations in mitochondrial (mt) DNA and/or nuclear (nuc) DNA in a somatic cell early in development that adversely effect mito chondrial function, 2) mutations in maternal mtDNA and/or nucDNA that impair mitochondria in offspring, 3) mutations in the amyloid precurso r protein (APP), and 4) increased formation of both normal APP and sup eroxide dismutase (SOD). The incidence of SDAT may be decreased by eff orts to minimize free radical reactions involved in initiation. The cl inical decline of SDAT patients may be slowed by measures which lower the level of more-or-less random deleterious free radical reactions.