Calbindin D-28k and Monoamine Oxidase A Immunoreactive Neurons in the Nucleus Basalis of Meynert in Senile Dementia of the Alzheimer Type and Parkinson's Disease

Abstract

In this study, calbindin D-28k (CaBP), monoamine oxidase A (MAO A) and nerve growth factor receptor (NGFr) immunoreactivities were investigated in the nucleus basalis of Meynert (NbM) in patients with senile dementia of the Alzheimer type (SDAT), with Parkinson''s disease (PD) with or without dementia, and in controls. Immunocytochemistry using specific antibodies in differing serial sections was employed, and cell counts and NbM nuclear volume measurements were made. Most of the large multipolar NbM neurons showed CaBP immunoreactivity in the cytoplasm of their somata, dendrites and axons. In adjacent, NGFr-reacted sections, the large NbM neurons were also found to be intensely immunoreactive for NGFr on their cellular surfaces. In addition, a subpopulation of large NbM neurons and glial cells were found to be immunoreactive for MAO A. The number of CaBP-immunoreactive (CaBP-i) neurons was decreased by an average of 55% in the 6 SDAT patients, 70% in the 2 nondemented PD patients and 40% in the 1 demented PD patient. The volume calculated for the compact part of the NbM formed by the CaBP-i neuronal somata decreased by an average of 47% in SDAT. On the other hand, measurements in the volume of NGFr-i neurons (including the dendritic arborization) showed an average decrease of 25% in SDAT patients compared to controls. Although all SDAT and PD patients showed a decrease of CaBP-i neurons in the NbM, a loss of MAO-A-i NbM neurons was found only in those patients with dementia. Therefore, the relative proportions of MAO-A-i to CaBP-i neurons were increased in the nondemented PD patients (14.2 and 19.6%) when compared with those in the demented PD patient (2.2%) and with the SDAT patients (0.3-5.6%). These data indicate that a balanced presence of MAO-A-i cholinergic, large NbM neurons may be necessary for the proper maintenance of cognitive function. Functionally this may be translated to mean that dementing changes may cause a decrease from the normal amount of MAO A enzyme activity. This suggests that therapeutic strategies based upon correction of MAO-A activities by MAO-A inhibitors may be important to ameliorating some of the loss in cholinergic function in dementias of SDAT and PD.

Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer's disease. II. Ageing, Korsakoff's disease, Parkinson's disease, and Alzheimer's disease

“…In cases of PD with moderate and severe dementia, neuronal loss reached an extent that was similar to that observed in AD. This is in agreement with other studies (Buttlar-Brentano, 1955;Arendt et al, 1983;Candy et al, 1983;Whitehouse et al, 1983;Gaspar and Gray, 1984;Tagliavini et al, 1984;Jellinger, 1986;Mufson et al, 1991;Chan-Palay et al, 1993).…”

Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer’s disease (Review)

“…Furthermore, MAO-A activity appears to be lower in the locus ceruleus in patients with AD, and is accompanied by an ~80% decrease in the number of neurons (78), revealing that activated MAO-A in neurons is involved in the pathology of this disease as a predisposing factor. In comparison, increased MAO-A activity appeared more significant in the glia of patients with AD (79). Thus, the changes in MAO-A levels in patients with AD appear to have multiple mechanisms.…”

Recent Developments in the Regulation of Monoamine Oxidase Form and Function: Is the Current Model Restricting Our Understanding of the Breadth of Contribution of Monoamine Oxidase to Brain [dys]Function?

“…MAO-A activity and MAO-A mRNA are also reported to be elevated in several areas of the AD brain including the occipital cortex, frontal lobe of neocortex, parietal cortex, and locus coeruleus [93,95,96] as well as in the caudate nucleus, thalamus and white matter [97]. Although there are also reports of decreases in MAO-A activity in AD brains [95,98], it is important to realize that a substantial amount of MAO-A (i.e. 75-80%) needs to be inhibited before any effects on MAO-A-mediated cell function would be notable [99,100].…”

“…75-80%) needs to be inhibited before any effects on MAO-A-mediated cell function would be notable [99,100]. Furthermore, the 17-31% decrease in MAO-A activity in the AD locus coeruleus, where nearly 70~80% of the neurons are lost [95,98,101], suggests that the average MAO-A activity per surviving neuron is actually increased [95]. Such a localized hyperactivation of MAO-A could certainly account for the accumulation of toxic MAO-mediated metabolites in AD brains [102].…”