Neuronal Loss Is Greater in the Locus Coeruleus Than Nucleus Basalis and Substantia Nigra in Alzheimer and Parkinson Diseases

Department of Neurology, University of Southern California, Los Angeles, CA, USA.
JAMA Neurology (Impact Factor: 7.42). 03/2003; 60(3):337-41. DOI: 10.1001/archneur.60.3.337
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Alzheimer disease (AD) and Parkinson disease (PD) are associated with neuronal degeneration in major subcortical nuclei, but few studies have examined the neuronal degeneration in these nuclei concurrently.
To identify clinical and pathological correlates of neuronal loss in the nucleus basalis (NB), locus coeruleus (LC), and substantia nigra pars compacta (SN) in AD and PD.
The study sample comprised 86 cases with pathologically confirmed AD, 19 cases with PD, and 13 healthy elderly control subjects. The number of nucleolated neurons was counted in representative sections of the NB, LC, and SN. Effect sizes (ES) were computed to determine the standardized difference in cell counts relative to healthy controls.
Cases of AD showed the greatest neuronal loss in the LC (ES = 3.16) followed by the NB (ES = 1.10), but variable loss in the SN (ES = 0.16). Cases of PD also showed the greatest neuronal loss in the LC (ES = 6.47), followed by the SN (ES = 2.58) and the NB (ES = 0.85). Significant correlations were found between the number of neurons in the NB and LC in PD (r = 0.54, P<.05), as well as AD (r = 0.24, P<.05). The duration of illness correlated with greater neuronal loss in the LC and NB in AD, and greater neuronal loss in the SN in PD.
For both AD and PD the greatest neuronal loss was found in the LC. In AD, neuronal loss was most severe and best correlated with the duration of illness in the LC, rather than in NB as traditionally expected. Correlations between neuronal loss in the LC and NB (but not SN) in both PD and AD suggest that the former 2 nuclei may share common pathogenetic susceptibilities. Given the prominent loss of neurons in the LC, detection and treatment of noradrenergic deficiencies warrant attention in both AD and PD.

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    • "The majority of LC noradrenergic neurons are lost in AD, PD, and DLB (Brunnström et al. 2011), to a lesser extent in FTLD (Brunnström et al. 2011), and morphological and histological changes occur in LC of ALS patients as well (Hoogendijk et al. 1995) (Iwanaga et al. 1997). Recently, it was reported that neuron loss in LC of AD and PD patients is even greater than that observed in regions of the forebrain and substantia nigra, respectively (Zarow et al. 2003). Anatomist Heiko Braak has written extensively on his findings regarding the stages of the pathological process in both AD and PD, and in both cases it is clear that LC pathology occurs long before most other regions incur damage (Braak et al. 2011)(Braak et al. 2004)(but see (Burke et al. 2008) for an alternative view). "
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    SpringerPlus 12/2015; 4(1):25. DOI:10.1186/s40064-014-0777-6
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    • "Thus, DA may exert its toxicity through oxidation to DA-quinone followed by binding to SH enzymes that are essential for cell proliferation and/or survival. PD selectively targets catecholaminergic neurons, with a variable degree of involvement of the LC compared to the SN (Paulus and Jellinger 1991; Gesi et al. 2000; Zarow et al. 2003; Cebrian et al. 2014). It was clearly shown that patients with PD show a severe decrease of "
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    • "Damage and loss of LC noradrenergic neurons are accelerated in certain progressive neurodegenerative diseases, such as Alzheimer's Diseases (AD) (Mann et al. 1983; Bondareff et al. 1987; German et al. 1992; Grudzien et al. 2007) and Parkinson's Diseases (PD) (Mann and Yates 1983; Arima and Akashi 1990; Chan-Palay 1991b; Forno 1996), which are early pathological indicators of these diseases. The greater neuronal loss was observed in the LC (83 % loss in AD; 68 % loss in PD) compared with other subcortical nuclei (the nucleus basalis and substantia nigra pars compact ) (Lyness et al. 2003; Zarow et al. 2003), and correlated to a reduced level of NE in the brain (Adolfsson et al. 1979; Palmer and DeKosky 1993). However, despite extensive studies of AD and PD, it remains unclear why degeneration of the LC neurons precedes those neurons observed in other subcortical nuclei in these diseases. "
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