Evidence for angiogenesis in Parkinson’s disease, incidental Lewy body disease, and progressive supranuclear palsy

Angiogenesis has not been extensively studied in Parkinson’s disease (PD) despite being associated with other neurodegenerative disorders. Post-mortem human brain tissues were obtained from subjects with pathologically confirmed Parkinson’s disease (PD) and progressive supranuclear palsy (PSP), a rapidly progressing Parkinsonian-like disorder. Tissues were also obtained from subjects with incidental Lewy body disease (iLBD) who had Lewy bodies in the substantia nigra pars compacta (SN_pc) but had not been diagnosed with PD, and age-matched controls without Lewy body pathology. The SNpc, putamen, locus ceruleus (LC) and midfrontal cortex were examined for integrin αvβ3, a marker for angiogenesis, along with vessel number and activated microglia. All parkinsonian syndromes had greater αvβ3 in the LC and the SN_pc, while only PD and PSP subjects had elevated αvβ3 in the putamen compared to controls. PD and PSP subjects also had increases in microglia number and activation in the SN_pc suggesting a link between inflammation and clinical disease. Microglia activation in iLBD subjects was limited to the LC, an area involved at an early stage of PD. Likewise, iLBD subjects did not differ from controls in αvβ3 staining in the putamen, a late area of involvement in PD. The presence of αvβ3 reactive vessels in PD and its syndromes is indicative of newly created vessels that have not likely developed the restrictive properties of the blood brain barrier. Such angiogenic vessels could contribute to neuroinflammation by failing to protect the parenchyma from peripheral immune cells and inflammatory or toxic factors in the peripheral circulation.