Dementia With Lewy Bodies - Pathophysiology

Pathophysiology

Pathologically, DLB is characterized by the development of abnormal proteinaceous (alpha-synuclein) cytoplasmic inclusions, called Lewy bodies, throughout the brain. These inclusions have similar structural features to "classical" Lewy bodies seen subcortically in Parkinson's disease. Additionally, a loss of dopamine-producing neurons (in the substantia nigra) occurs, similar to that seen in Parkinson's disease, and a loss of acetylcholine-producing neurons (in the basal nucleus of Meynert and elsewhere) similar to that seen in Alzheimer's disease. Cerebral atrophy (or shrinkage) also occurs as the cerebral cortex degenerates. Autopsy series have revealed the pathology of DLB is often concomitant with the pathology of Alzheimer's disease. That is, when Lewy body inclusions are found in the cortex, they often co-occur with Alzheimer's disease pathology found primarily in the hippocampus, including senile plaques (deposited beta-amyloid protein), and granulovacuolar degeneration (grainy deposits within and a clear zone around hippocampal neurons). Neurofibrillary tangles (abnormally phosphorylated tau protein) are less common in DLB, although they are known to occur, and astrocyte abnormalities are also known to occur. It is presently not clear whether DLB is an Alzheimer's variant or a separate disease entity. Unlike Alzheimer's disease, the brain may appear grossly normal with no visible signs of atrophy.