Neuropathology of Alzheimer\u27s Disease and the Lewy Body Variant of Alzheimer\u27s Disease: Synapse Density and Pathological Staging: New Pieces of the Puzzle

The dementing disorders are a heterogeneous group of diseases with respect to their neuropatho-logic features and etiologies. Dementia is most commonly associated with the neurodegenerative disorders: conditions characterized by the dysfunction and death of specific, selectively vulnerable populations of neurons in the brain. The selective vulnerability of the neurons at risk in a given disorder may be based upon their location in the nervous system, shared biochemical properties (e.g., widely distributed neurons all using the same neurotransmitter), or some other, perhaps as yet undetermined, factor(s). The degenerative dementias are typically insidious in onset and slowly progressive. Another feature shared by most of the degenerative disorders is that their etiology, or cause, is unknown; i.e., the conditions are idiopathic. For most, there is no clinical test to diagnose the disorder with certainty, and a definitive diagnosis depends upon the appropriate clinical history followed by microscopic examination of brain tissue. This review will briefly summarize the well-documented neuropathologic features of Alzheimer’s disease (AD) and the Lewy body variant of Alzheimer’s disease (LBV) and highlight new directions and recent advances in the understanding of AD. Specifically, the significance of loss of synapses as a mechanism for the insidious cognitive decline seen in AD and the role of pathological staging will be addressed