Skip to main content
SpringerLink
Log in

Selective loss of nigral neurons in Alzheimer's disease: a morphometric study

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Loss of neurons from the substantia nigra (SN), which is sometimes observed in Alzheimer's disease (AD), was quantitatively analyzed in 10 cases of presenile AD and 19 age-matched controls. On sections from the upper and lower portions of the SN, the pigmented zone (zona compacta) and the nonpigmented zone (zona reticulata) were delineated, and these zones were partitioned into quarters: medial, mid-medial, mid-lateral and lateral. This approach clarified topographical preference of neuronal depletion in the SN of AD; namely (1) pigmented neurons were more severely affected than non-pigmented neurons, (2) neuronal depletion was more marked in the lower SN (−38%, P<0.001), where the pigmented neurons in the medial quarter were most severely affected (−51%, P<0.001), (3) in the upper SN (neuronal loss: −21%, P <0.01), the pigmented neurons in the mid-medial quarter were most severely affected (−43%, P<0.01). These findings suggest that some groups of nigral neurons are primarily involved in presenile AD. Gallyas staining after bleaching of melanin pigments uncovered a large number of neurofibrillary tangles (NFTs) mainly in the pigmented zone, especially in the medial quarter. A large number of NFTs, scarse senile plaques, and substantial depletion of neurons form an unique combination of Alzheimer pathology in the SN not well recognized so far.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bogerts B, Häutsch J, Herzer M (1983) A morphometric study of the dopamine-containing cell groups in the mesencephalon of normals, Parkinson patients and schizophrenics. Biol Psychiatry 18:951–969

    Google Scholar 

  2. Braak H, Braak E, Ohm T, Bohl J (1988) Silver impregnation of Alzheimer's neurofibrillary changes counterstained for basophilic material and lipofuscin pigment. Stain Technol 63:197–200

    Google Scholar 

  3. Chui HC, Mortimer JA, Slager U, Zarow C, Bondareff W, Webster DD (1986) Pathologic correlates of dementia in Parkinson's disease. Arch Neurol 43:991–995

    Google Scholar 

  4. Ditter SM, Mirra SS (1987) Neuropathologic and clinical features of Parkinson's disease in Alzheimer's disease patients. Neurology 37:754–760

    Google Scholar 

  5. German DC, White III CL, Sparkman DR (1987) Alzheimer's disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neuroscience 21:305–312

    Google Scholar 

  6. German DC, Manaye K, Smith WK, Woodward DJ, Saper CB (1989) Midbrain dopaminergic cell loss in Parkinson's disease: computer visualization. Ann Neurol 26:507–514

    Google Scholar 

  7. Gibb WRG, Lees AJ (1991) Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease. J Neurol Neurosurg Psychiatry 54:388–396

    Google Scholar 

  8. Gibb WRG, Mountjoy CQ, Mann DMA, Lees AJ (1989) The substantia nigra and ventral tegmental area in Alzheimer's disease and Down's syndrome. J Neurol Neurosurg Psychiatry 52:193–200

    Google Scholar 

  9. Greenfield JG, Bosanquet FD (1953) The brain-stem lesions in Parkinsonism. J Neurol Neurosurg Psychiatry 16:213–226

    Google Scholar 

  10. Hassler R (1938) Zur Pathologie der Paralysis agitans und des postenzephalitischen Parkinsonismus. J Psychol Neurol 48:387–476

    Google Scholar 

  11. Hirano A, Zimmerman HM (1962) Alzheimer's neurofibrillary changes: a topographic study. Arch Neurol 7:227–242

    Google Scholar 

  12. Hirsch E, Graybiel AM, Agid YA (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 334:345–348

    Google Scholar 

  13. Ishii T (1966) Distribution of Alzheimer's neurofibrillary changes in the brain stem and hypothalamus of senile dementia. Acta Neuropathol (Berl) 6:181–187

    Google Scholar 

  14. Jellinger K (1987) Quantitative changes in some subcortical nuclei in aging, Alzheimer's disease and Parkinson's disease. Neurobiol Aging 8:556–561

    Google Scholar 

  15. Jellinger K (1987) Neuropathological sustrates of Alzheimer's disease and Parkinson's disease. J Neural Transm [Suppl] 24:109–129

    Google Scholar 

  16. Jellinger K (1989) Pathology of Parkinson's syndrome. In: Calne DB (ed) Handbook of experimental pharmacology, vol 88. Springer, Berlin, pp 47–112

    Google Scholar 

  17. Joachim CL, Morris JH, Selkoe DJ (1988) Clinically diagnosed Alzheimer's disease: autopsy results in 150 cases. Ann Neurol 24:50–56

    Google Scholar 

  18. Klaue R (1940) Parkinsonsche Krankheit (Paralysis agitans) und postencephalitischer Parkinsonismus: Vergleich einer klinisch-anatomischen Differentialdiagnose. Arch Psychiatr Nervenkr 111:251–321

    Google Scholar 

  19. Lai F, Williams RS (1989) A prospective study of Alzheimer disease in Down syndrome. Arch Neurol 46:849–853

    Google Scholar 

  20. Leverenz J, Sumi SM (1986) Parkinson's disease in patients with Alzheimer's disease. Arch Neurol 43:662–664

    Google Scholar 

  21. Mann DMA, Yates PO, Marcynuik B (1984) Monoaminergic neurotransmitter systems in presenile Alzheimer's disease and in senile dementia of Alzheimer type. Clin Neuropathol 5:199–205

    Google Scholar 

  22. Mann DMA, Yates PO, Marcynuik B (1987) Dopaminergic neurotransmitter system in Alzheimer's disease and in Down's syndrome at middle age. J Neurol Neurosurg Psychiatry 50:341–344

    Google Scholar 

  23. Mölsä PK, Marttila RJ, Rinne UK (1984) Extrapyramidal signs in Alzheimer's disease. Neurology 34:1114–1116

    Google Scholar 

  24. Morris JC, Drazner M, Fulling K, Grant A, Goldring J (1989) Clinical and pathological aspects of Parkinsonism in Alzheimer's disease: a role for extranigral factors? Arch Neurol 46:651–657

    Google Scholar 

  25. Olszewski J, Baxter D (1982) Cytoarchitecture of the human brain stem, 2nd edn. Karger, Basel New York, pp 50–56

    Google Scholar 

  26. Oyanagi K, Takeda S, Takahashi H, Ohama E, Ikuta F (1989) A quantitative investigation of the substantia nigra in Huntington's disease. Ann Neurol 26:13–19

    Google Scholar 

  27. Pakkenberg H, Brody H (1965) The number of nerve cells in substantia nigra in paralysis agitans. Acta Neuropathol (Berl) 5:320–324

    Google Scholar 

  28. Pakkenberg B, Møller A, Grundersen HJG, Dam AM, Pakkenberg H (1991) The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson's disease estimated with an unbiased stereological method. J Neurol Neurosurg Psychiatry 54:30–33

    Google Scholar 

  29. Pearce J (1974) The extrapyramidal disorder of Alzheimer's disease. Eur Neurol 12:94–103

    Google Scholar 

  30. Rinne JO, Rummukainen J, Paljärvi L, Rinne UK (1989) Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra. Ann Neurol 26:47–50

    Google Scholar 

  31. Saper CB, Wainer BH, German DC (1987) Axonal and transneuronal transport in the transmission of neurological disease: potential role in system degenerations, including Alzheimer's disease. Neuroscience 23:389–398

    Google Scholar 

  32. Tabaton M, Schenone A, Romagnoli P, Mancardi GL (1985) A quantitative and ultrastructural study of substantia nigra and nucleus centralis superior in Alzheimer's disease. Acta Neuropathol (Berl) 68:218–223

    Google Scholar 

  33. Tomlinson BE, Corsellis JAN (1984) Ageing and the dementias. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greenfield's neuropathology, 4th edn. Arnold, London, p 981

    Google Scholar 

  34. Tyrrell PJ, Rossor MN (1989) Extrapyramidal signs in dementia of Alzheimer type. Lancet II:920

    Google Scholar 

  35. Uchihara T, Tsuchiya K, Kosaka (1990) Selective loss of nigral neurons in Pick's disease: a morphometric study. Acta Neuropathol 81:155–161

    Google Scholar 

  36. Vieregge P, Ziemens G, Freudenberg M, Piosinski A, Muysers A, Schulze B (1991) Extrapyramidal features in advanced Down's syndrome: clinical evaluation and family history. J Neurol Neurosurg Psychiatry 54:34–38

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuropathology, Psychiatric Research Institute of Tokyo, 2-1-8 Kamikitazawa, Setagaya-ku, 152, Tokyo, Japan

    T. Uchihara, H. Kondo & K. Kosaka

  2. Department of Neurology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113, Tokyo, Japan

    T. Uchihara & H. Tsukagoshi

  3. Department of Psychiatry and Neurology, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, 236, Yokonama, Japan

    K. Kosaka

Authors
  1. T. Uchihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Kosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Tsukagoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Uchihara, T., Kondo, H., Kosaka, K. et al. Selective loss of nigral neurons in Alzheimer's disease: a morphometric study. Acta Neuropathol 83, 271–276 (1992). https://doi.org/10.1007/BF00296789

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00296789

Key words

Search

Navigation