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
Source: PubMed


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.

Download full-text


Available from: Scott A Lyness
  • Source
    • "The toxicity results from the facile autoxidation of these intermediates, thus producing reactive oxygen species. 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; Cebri an et al. 2014). It was clearly shown that patients with PD show a severe decrease of NM levels in their SN (around 60% compared to age-matched controls) due to the loss of neurons containing NM (Zecca et al. 2002). "

    Full-text · Dataset · Dec 2015
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sleep/wake disturbance is a feature of almost all common age-related neurodegenerative diseases. Although the reason for this is unknown, it is likely that this inability to maintain sleep and wake states is in large part due to declines in the number and function of wake-active neurons, populations of cells that fire only during waking and are silent during sleep. Consistent with this, many of the brain regions that are most susceptible to neurodegeneration are those that are necessary for wake maintenance and alertness. In the present review, these wake-active populations are systematically assessed in terms of their observed pathology across aging and several neurodegenerative diseases, with implications for future research relating sleep and wake disturbances to aging and age-related neurodegeneration.
    Full-text · Article · Dec 2015 · SpringerPlus
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: In order to elucidate the chemical structure of black to brown pigments, neuromelanins (NMs), in the substantia nigra (SN) and the locus coeruleus (LC) in the central nervous system of humans and other mammalian species during aging, chemical degradative methods are powerful tools. HPLC analysis after hydroiodic acid hydrolysis detected aminohydroxyphenylethylamines, aminohydroxyphenylacetic acids, and aminohydroxyethylbenzenes, which confirmed that SN-NM and LC-NM contain melanin derived not only from dopamine and norepinephrine (NE) but also from several other catecholic metabolites, such as 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxymandelic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylethylene glycol, in addition to the corresponding Cys-derivatives in varying degrees. However, hydroiodic acid hydrolysis showed that LCNM produced the same degradation products as were detected in SN-NM. Thus, we needed to develop a new chemical detection method to validate the existence of NE in LC-NM. In the present study, we report that HCl hydrolysis of LC-NM in the presence of thioglycolic acid yields new products arising from substitution of the hydroxyl group by thioglycolic acid at the benzyl position of NE and cysteinyl-NE. This is the first chemical evidence showing that NE and cysteinyl-NE are incorporated into LC-NM.
    Full-text · Article · Nov 2015 · Journal of Neurochemistry
Show more