Intermediary metabolism disturbance in AD/SDAT and its relation to molecular events.

1. Early-onset dementia of Alzheimer type (EODAT; AD) and late-onset dementia of Alzheimer type (LODAT; SDAT) are heterogenous in origin. 2. A common superordinate pathobiochemical principle in the etiopathogenesis of both types of dementia is neuronal energy failure with subsequent abnormalities in cellular Ca2+ homeostasis and glucose-related amino acid metabolism. 3. These metabolic abnormalities are assumed to occur first at axodendritic terminals of the acetylcholinergic-glutamatergic circuit and to cause morphological damage at synaptic sites. 4. Metabolic stress and structural damage at synaptic sites may induce enhanced formation of APP and its cleavage product amyloid. 5. Energy-metabolism related abnormalities along with functional and structural changes at synaptic sites of the acetylcholinergic-glutamatergic circuit may precede the formation of amyloid in DAT brain.