Figure 2.

CB₁ cannabinoid receptor distribution in aged human hippocampus and in Alzheimer’s disease. (A) Schema of the human hippocampal formation. Open rectangles identify the general location of images in B and E. (B) CB₁ cannabinoid receptor (CB₁R) immunoreactivity overlaps with synaptophysin⁺ nerve terminals targeting the perisomatic region (C) as well as apical dendrites (D) of Ammon’s horn 1 pyramidal neurons. High-resolution microscopy reveals CB₁ cannabinoid receptor⁺/synaptophysin⁺ terminals (arrowheads) around pyramidal cell perikarya (C–C₃) and dendrites (D–D₃). Note the mutually exclusive localization of CB₁ cannabinoid receptors and MAP2⁺ dendrites. Dashed lines encircle neuronal somata (C) and dendrite (D). Asterisks in C are overlain on neuronal nuclei. (E) CB₁ cannabinoid receptor⁺ afferents engulf cells in the granular layer abundantly immunoreactive for amyloid-β_17-24 [Aβ(17–24)], likely localizing intracellular amyloid precursor protein, as well as amyloid-β_17–24⁺ senile plaque (open rectangle). (E₁–E₃) The density of CB₁ cannabinoid receptor⁺ axons and synapses appear unchanged in the proximity of senile plaques. Instead, CB1 cannabinoid receptor⁺ processes appear to accumulate locally around, and even penetrate senile plaques (arrows). CA = Ammon’s horn; DF = dentate fascia; sub = subiculum. Scale bars = 20 μm (B, E and E₃), 12 μm (C₃), 4 μm (D₃).