Correlates of hippocampal neuron number in Alzheimer's disease and ischemic vascular dementia

Abstract

The cornu ammonis 1 region of the hippocampus (CA1) sector of hippocampus is vulnerable to both Alzheimer's disease (AD)-type neurofibrillary degeneration and anoxia-ischemia. The objective of this article is to compare number and size of neurons in CA1 in AD versus ischemic vascular dementia. Unbiased stereological methods were used to estimate the number and volume of neurons in 28 autopsy-derived brain samples. For each case, the entire hippocampus from one cerebral hemisphere was sliced into 5mm slabs (5-7 slabs/case), cut into 50 microm sections, and stained with gallocyanine. Using the optical dissector, we systematically sampled the number and size of neurons throughout the extent of CA1 and CA2. The total number of neurons was significantly less in AD compared with ischemic vascular dementia (p < 0.02), but there was no significant difference in neuron size. The greatest loss of neurons was observed in two cases with combined AD and hippocampal sclerosis. Regardless of causative diagnosis, the number of CA1 neurons correlates with magnetic resonance imaging-derived hippocampal volume (r = 0.72; p < 0.001) and memory score (r = 0.62; p < 0.01). We conclude that although CA1 neuron loss is more consistently observed in AD than ischemic vascular dementia, severity of loss shows the expected correlation with structure and function across causative subtype. Reductions in magnetic resonance imaging-derived hippocampal volume reflect loss, rather than shrinkage, of CA1 neurons.

Fig 1

Estimated number of neurons in cornu ammonis 1 region of the hippocampus (CA1) is strongly correlated with the estimated number of neurons in CA2. Stars indicate healthy control subjects; circles indicate cognitively impaired not meeting criteria for Alzheimer’s disease (AD); triangles indicate AD; squares indicate AD with hippocampal sclerosis; and diamonds indicate ischemic vascular dementia.

Fig 2

Estimated number of neurons in cornu ammonis 1 region of the hippocampus (CA1) is strongly correlated with the volume of the hippocampus determined from magnetic resonance imaging. Stars indicate healthy control subjects; circles indicate cognitively impaired not meeting criteria for Alzheimer’s disease (AD); triangles indicate AD; squares indicate AD with hippocampal sclerosis; and diamonds indicate ischemic vascular dementia. MRI = magnetic resonance imaging.

Fig 3

Number of neurons in cornu ammonis 1 region of the hippocampus (CA1) versus Braak score. Stars indicate healthy control subjects; circles indicate cognitively impaired not meeting criteria for Alzheimer’s disease (AD); triangles indicate AD; squares indicate AD with hippocampal sclerosis; and diamonds indicate ischemic vascular dementia.

Fig 4

Number of neurons versus memory scores. Stars indicate healthy control subjects; circles indicate cognitively impaired not meeting criteria for Alzheimer’s disease (AD); triangles indicate AD; squares indicate AD with hippocampal sclerosis; and diamonds indicate ischemic vascular dementia.