Neuropathological changes in the nucleus basalis correlate with clinical measures of dementia.

The present study correlates the severity of dementia in Alzheimer's disease with the degree of neuropathology present in the nucleus basalis of Meynert. We assessed neurofibrillary tangles, neuronal loss and morphometric changes in 21 patients with Alzheimer's disease who underwent extensive neuropsychological testing before death. We report a highly significant correlation between scores in the psychological tests and all of the neuropathological markers examined within the nucleus basalis of Meynert. The test that correlated most closely with these morphological measures was Folstein's Mini Mental State. Among the different neuropathological changes, the number of neurofibrillary tangles was strongly correlated with the degree of dementia. We also provide evidence for a differential involvement of the three subdivisions of the nucleus basalis in Alzheimer's disease neuropathology. The posterior subdivision, which provides a substantial cholinergic input to the parahippocampal gyrus, was the more profoundly affected. Taken together, these results point to an important participation of the nucleus basalis in dementia of the Alzheimer type. In addition, the strong correlation between neuropathological changes and neuropsychological scores indicates the reliability of these tests in assessing the progression of the disease.

Cell loss in supraoptic and paraventricular nucleus in Alzheimer's disease.

Previous studies have shown an activation of the hypothalamo-neurohypophyseal system (HNS) in normal aging and in senile dementia. Among other explanations, this activation might be secondary to cell loss in the supraoptic (SO) and paraventricular (PV) nuclei. This study reports a 63% loss in the SO and a 56% loss in the PV in a group of Alzheimer disease (AD) patients. The remaining neurons undergo a compensatory hypertrophy that is more pronounced in the SO, affecting cell and nuclear size as well as nucleolar volume. The group of patients with a diagnosis of moderate dementia showed the greatest hypertrophy, as compared to the severely demented patients. Our results suggest that there is a compensatory capacity in the earlier stages of the dementia, that is lost in the final stages of Alzheimer's disease.

Calbindin D-28k immunoreactivity in the temporal neocortex in patients with Alzheimer's disease.

Calbindin D-28k immunoreactivity in the temporal isocortex was examined in seven patients with Alzheimer's disease (AD) and in six controls. In normal brains, calbindin D-28k-immunoreactive cells were bitufted neurons, multipolar cells with ascending dendrites and large double-bouquet cells mainly located in layers II and III. Immunoreactive fibres were seen in the molecular layer and in vertical bundles in layers III and V/VI. Calbindin D-28k immunoreactivity was reduced in patients with AD, although with differences from one patient to another. Immunoreactivity was decreased in the plexus of the molecular layer and in the vertical bundles in the cellular layers in every case. Most patients had, also, decreased immunoreactivity in the dendritic arbors. The number of calbindin D-28k-immunoreactive cells was significantly decreased in three of five patients with moderate or severe dementia, and was normal in two cases with mild dementia.

Calbindin immunoreactivity in normal human temporal neocortex.

Calbindin immunoreactivity in the temporal neocortex was examined in 4 subjects with no neurological, metabolic or malignant disease. The brains were obtained between 1 and 4 h after death and rapidly fixed by perfusion with 4% paraformaldehyde through the carotid arteries, cut into slabs, cryoprotected and stored at -80 degrees C. Sections of the whole left temporal lobe obtained with a freezing microtome were processed free-floating with a well known monoclonal antibody against calbindin according to the peroxidase-antiperoxidase (PAP) method. Calbindin-immunoreactive (CaBP-ir) neurons were found to be local-circuit neurons (interneurons) mainly distributed in the upper cortical layers (layers I, II and III), and were categorized as small multipolar neurons with ascending dendrites ramifying in the molecular layer, small bitufted cells, pyramid-like cells in layer II, horizontal neurons in the molecular layer, multipolar neurons with long descending dendrites, and large double-bouquet cells, some of them exhibiting a very long dendrite with claw-shaped terminals in layer V. Less than 10% of all CaBP-ir neurons were localized in the remaining cortical layers. Pyramidal cells were only very weakly or not stained at all. In addition, CaBP-ir fibres formed a dense plexus in the molecular layer, and vertical bundles 8-10 microns thick and 500-600 microns long, separated by blank spaces 20-40 microns wide were distributed in layers III and V/VI.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential changes in cell size and number in topographic subdivisions of human basal nucleus in normal aging.

The age-related cell loss of the nucleus basalis of Meynert is of considerable importance because loss of its neurons may be followed by cognitive decline. Compared to the number found at ages 16-29 years, we found that 50% of the total population of neurons is lost by 90 years of age. This change in number is accompanied by modifications in the morphometric features, including a 17.3% increase in cell size by 60 years of age as compared with values at 16 years, and followed by a gradual decline. Topographic differences were seen both in the neuronal loss and in morphometry: in relation to the youngest group, the posterior subdivision is the most severely affected by 90 years (64.5% decrease in number and 10% reduction in neuronal size), followed by the intermediate subdivision (42% loss of neurons accompanied by 4% increase in cell size). In the anterior subdivision no significant decrease in the number of neurons could be detected, although a 15% increase in cell size occurred.

Cell loss and nuclear hypertrophy in topographical subdivisions of the nucleus basalis of Meynert in Alzheimer's disease.

The nucleus basalis of Meynert was examined in six patients with Alzheimer's disease and five age-matched controls. A cytoarchitectonic study was followed by quantitative analysis of the population of neurons and by the determination of their nuclear area. Confirming previous neuropathological observations in Alzheimer's disease, a neuronal loss of 43% in the anterior, 25% in the intermediate and 30.5% in the posterior subdivisions of the nucleus basalis of Meynert was observed. Numerous surviving cells showed neurofibrillary tangles. In addition, we found that the nuclear area of the remaining nucleus basalis of Meynert neurons was significantly increased in all three subdivisions by at least 16%. The combined observation of cell loss and nuclear hypertrophy suggests that both regenerative and degenerative changes co-exist in the nucleus basalis in Alzheimer's disease.