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Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits

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Abstract

Multiple reports have documented an age-related loss, estimated at about 10% per decade, of the pigmented neurons in the substantia nigra. This is associated with motor dysfunction, including bradykinesia, stooped posture and gait disturbance. As microglia are activated by cell death and neuromelanin pigment, we hypothesized that there should be a significant microglial reaction in normal aging human substantia nigra. Sections of substantia nigra from elderly subjects (N = 15; mean 81.3; SD 7.0) and younger subjects (N = 7; mean 30.3; SD = 8.7), all of which had no specific neurologically or neuropathologically defined disorders, were stained immunohistochemically for MHC Class II and the area occupied by microglia was quantified in substantia nigra pars compacta. All elderly subjects showed a pronounced microglial reaction in the substantia nigra, with frequent, intensely stained hypertrophic microglia, while immunoreactive nigral microglia were much less frequent in the younger subjects. Quantification showed that in older subjects, the percentage of substantia nigra area occupied by microglial bodies and processes was significantly greater than for younger subjects (mean 19.6 vs. 3.6; P = 0.005). Extraneuronal neuromelanin deposits were present in all the older subjects but were absent or rare in the younger subjects. The neuromelanin deposit abundance score in the older subjects correlated significantly with the area occupied by immunoreactive microglia. The marked microglial reaction in normal aging human substantia nigra, together with the previously reported 35–80% pigmented neuron loss, indicates the presence of a powerful pathologic process that may be additive with specific age-related neurodegenerative diseases, including Parkinson’s disease.

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Acknowledgments

This research is supported by grants to the Sun Health Research Institute Brain Donation Program and the Arizona Parkinson’s Disease Consortium by the Michael J. Fox Foundation for Parkinson’s Research (The Prescott Family Initiative), the Arizona Biomedical Research Commission (contracts 4001, 0011 and 05-901) and the National Institute on Aging (P30 AG19610).

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  1. Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA

    Thomas G. Beach, Lucia I. Sue, Douglas G. Walker, Lih Fen Lue, Donald J. Connor & Marwan N. Sabbagh

  2. Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA

    John N. Caviness & Charles H. Adler

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  1. Thomas G. Beach
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Correspondence to Thomas G. Beach.

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Beach, T.G., Sue, L.I., Walker, D.G. et al. Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits. Acta Neuropathol 114, 419–424 (2007). https://doi.org/10.1007/s00401-007-0250-5

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