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Neuronal densities and vascular pathology in the hippocampal formation in CADASIL
Yumi Yamamoto1, Yoshiki Hase2, Masafumi Ihara3
1Translational and Clinical Research Institute, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK; Department of Molecular Innovation in Lipidemiology, Suita, Osaka, Japan; Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) causes significant neuron loss in the hippocampus, contributing to memory deficits. This hereditary small vessel disease impacts specific neuron types, independent of infarcts.
Area of Science:
- Neurology
- Neuroscience
- Pathology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the primary hereditary cerebral small vessel disease.
- Hippocampal volume loss is a suspected mechanism for cognitive decline in CADASIL patients.
Purpose of the Study:
- To investigate neuronal loss in the hippocampal formation of CADASIL patients.
- To determine if specific neuron subsets are affected in CADASIL.
Main Methods:
- Unbiased stereological methods were employed to quantify neuron numbers and volumes.
- Neuronal counts (SMI32-positive and total) were compared between 12 CADASIL patients and age-matched controls.
Main Results:
- A 26%-50% reduction in SMI32-positive neuron densities was observed in the entorhinal cortex, layer V, and CA2 regions of CADASIL patients compared to young controls.
- Neuronal loss trends showed young controls > older controls ≥ CADASIL.
- These findings were independent of hippocampal infarcts, vascular pathology, or glial changes.
Conclusions:
- CADASIL is associated with significant loss of specific projection neuron subsets within the hippocampal formation.
- This neuronal loss likely contributes to memory deficits observed in CADASIL.
- The underlying arteriopathy may cause white matter damage, disrupting hippocampal networks.
Abstract:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral small vessel disease. Previous neuroimaging studies have suggested loss of hippocampal volume is a pathway for cognitive impairment in CADASIL. We used unbiased stereological methods to estimate SMI32-positive and total numbers and volumes of neurons in the hippocampal formation of 12 patients with CADASIL and similar age controls (young controls) and older controls. We found densities of SMI32-positive neurons in the entorhinal cortex, layer V, and cornu ammonis CA2 regions were reduced by 26%-50% in patients with CADASIL compared with young controls (p < 0.01), with a decreasing trend observed in older controls in the order of young controls> older controls ≥ CADASIL. These changes were not explained by any hippocampal infarct or vascular pathology or glial changes. Our results suggest notable loss of subsets of projection neurons within the hippocampal formation that may contribute to certain memory deficits in CADASIL, which is purely a vascular disease. It is likely that the severe arteriopathy leads to white matter damage which disconnects cortico-cortical and subcortical-cortical networks including the hippocampal formation.
