Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease.

Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatin-like immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia.

The high-affinity binding of thirteen ligands to putative neurotransmitter receptors was studied in temporal cortex of control and Alzheimer-type dementia (ATD) patients. A selective reduction of serotonin S2 receptors was observed in the ATD patients, to 57% of controls with no change in S1 receptors. Of the other ligand binding sites studied, only 3H-flunitrazepam binding was significantly reduced, to 84% of controls. Ligand binding sites which were unchanged in ATD temporal cortex included those labelled by adrenergic, adenosine, histamine, opiate, GABA, benzodiazepine and cholinergic ligands.

Auditory cortico-cortical connections in the owl monkey.

Two tonotopically organized cortical fields, the primary (A1) and rostral (R) fields, comprise a core of auditory cortex in the owl monkey. Injections of tritiated proline were made into each of these fields to determine their projections to the auditory fields in the ipsilateral and contralateral hemispheres using autoradiographic methods. Neurons in R project to the rostromedial (RM) and primary fields in both hemispheres, and to the posterolateral (PL) and anterolateral (AL) fields in the ipsilateral hemisphere. In addition, the rostral fields in the two hemispheres are connected. Neurons in the primary field project to RM and R in both hemispheres and to AL, Pl, and the caudomedial (CM) field in the ipsilateral hemisphere. The primary fields in the two hemispheres are connected. Single injections into A1 and R often result in labeling of two or more columns of tissue in the ipsilateral and contralateral target fields. Cortico-cortical axon terminations are concentrated in layer IV of fields AL and RM and in upper layer III and layer IV of R and CM. In A1, axon terminals of neurons whose cell bodies lie in A1 in the opposite hemisphere are concentrated in upper layer III and layer IV; axon terminals of neurons located in field R of the same hemispheres are concentrated in layers I and II. Layer IV of Pl contains the greatest concentration of cortico-cortical axon terminals; the supragranular layers contain a somewhat lower concentration. Neurons in R project contralaterally in the anterior commissure while A1 neurons send their axons contralaterally in the corpus callosum.

The brain ganglioside pattern in presenile and senile dementia.

Ganglioside lipid fractions in the cerebral gray matter were studied in 13 patients with various forms of dementia. In 2 patients with Alzheimer's disease and 1 with senile dementia an abnormal ganglioside pattern was observed, i.e., a decrease of G1 and G3 in association with an increase of G2. In the light of the total clinical and histologic data on the patients, it would seem that this disturbance in ganglioside metabolism may be a phenomenon accompanying extensive degradation of brain tissue rather than a factor in the etiology of dementia.

Ganglioside pattern of normal human brain, from samples obtained at surgery. A study especially referred to alkali labile species.

The ganglioside pattern from normal human temporal cortex and cerebellum has been studied in fresh specimens obtained at surgery. The analyses have been performed by two-dimensional thin layer chromatography with an intermediate ammonia treatment which is a methodology particularly suitable for resolving alkali labile gangliosides. Alkali labile gangliosides were detected in all the analyzed specimens and their content contributed to 23% and 11% of total lipid bound sialic acid, in temporal cortex and cerebellum, respectively.

Monoaminergic innervation of the frontal and temporal lobes in Alzheimer's disease.

Seven markers of ascending (corticopetal) dopaminergic, noradrenergic and serotonergic neurones and choline acetyltransferase activity have been studied postmortem in frontal and temporal cortex from subjects with Alzheimer's disease and compared with a matched group of controls. Dopaminergic neurones (concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid) were not deficient but some markers of the other neurones were affected. Noradrenaline and serotonin concentrations were reduced whereas the concentrations of their metabolites were either unaltered (5-hydroxyindoleacetic acid) or increased (3-methoxy-4-hydroxyphenylglycol). All deficits were most pronounced in the temporal cortex. Severely demented subjects had evidence of generalized neuronal loss, whereas those with moderate dementia showed significant loss of only choline acetyltransferase activity. In Alzheimer subjects, a significant relationship (inverse) was found between 5-hydroxyindoleacetic acid concentration and the number of neurofibrillary tangles.

Free amino acids in the brain of patients with Parkinson's disease.

To study free brain amino acids and their relation to dementia, the levels of glutamate, glutamate, asparagine, aspartate, glycine, taurine, homocarnosine and gamma-aminobutyric acid were determined in the temporal cortex and caudate nucleus in demented and non-demented patients with Parkinson's disease. In the temporal cortex, the levels of aspartate and asparagine were significantly increased in non-demented parkinsonian patients as compared both to demented patients and to controls. In the caudate nucleus no significant changes in amino acid levels were seen. Thus, the cortical and striatal glutamate/aspartate systems seem to be preserved in dementia in Parkinson's disease.

Decreased glutamic acid and increased 5-hydroxytryptamine in Huntington's disease brain.

gamma-Aminobutyric acid (GABA), glutamate and serotonin (5-HT), along with its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), have been measured in 4 brain regions taken post-mortem from patients with Huntington's disease and from control subjects. GABA was found to be significantly reduced, not only in the basal ganglia, but also in the cortex and hippocampus. Glutamate was also reduced in all regions except the pallidum, and thus was unrelated to the GABA deficit which was greatest in this area. 5-HT and 5-HIAA were significantly increased in all areas except the hippocampus.

High-molecular-weight forms of somatostatin are reduced in Alzheimer's disease and Down's syndrome.

Four molecular forms of somatostatin-like immunoreactivity (SOM-LI) are present in the human temporal cortex: SOM-14, SOM-28 and high-molecular-weight forms (HMW-SOM) of 7500 and 12,000 daltons. SOM-14 and HMW-SOM are depleted in cortical tissue from cases of pre-senile Alzheimer-type dementia (ATD), but there is a disproportionate reduction in HMW-SOM. In cases of Down's syndrome (DS) with the neuropathological and neurochemical changes of ATD, the total concentration of SOM-LI was similar to that in control cases and the proportions of molecular forms present were comparable. However, there was a significant reduction in the concentration of HMW-SOM. These results show that ATD and DS may share a common abnormality in the biosynthesis and/or post-translational processing of cortical SOM.

Immunohistochemical quantification of the synapse-related protein synaptophysin in Alzheimer disease.

Alzheimer disease (AD) as well as other dementing disorders are characterized by a continuous loss of neurons in cortical and subcortical areas and probably by an extensive synaptic loss. In order to substantiate and localize the loss of synapses in AD, we quantified by microdensitometry the neuropil immunoreactivity to an antibody that labels the protein synaptophysin (p38), which is localized in the presynaptic terminals. We found in the AD cases an average 50% decrease in the density of the granular neuropil immunoreaction in parietal, temporal and midfrontal cortex. In contrast, Pick disease cases presented close to normal values in parietal cortex, but major losses in temporal and frontal cortex. Our data strongly suggest an important role of synapse loss in dementia.

Reductions in soluble brain proteins in older subjects with Down's syndrome.

Soluble proteins from temporal cortex and caudate nucleus from 6 cases of Down's syndrome (5 aged over 50 and 1 aged 27 years) and 7 controls were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. In older Down's syndrome cases, reductions in tubulin and 5 other proteins were observed in cortex which had the neuropathology of Alzheimer's disease but not in caudate nucleus. No protein changes or neuropathological features of Alzheimer's disease were found in the youngest Down's syndrome case. The protein changes appear to be associated with the neuropathological features of Alzheimer's disease and not with Down's syndrome itself.

Neurotensin immunoreactivity in post-mortem brain is increased in Down's syndrome but not in Alzheimer-type dementia.

Neurotensin immunoreactivity and choline acetyltransferase (ChAT) activity were measured in post-mortem brain from 10 cases of Down's syndrome (7 aged 53-63 years, one aged 27 years, one aged 16 months and one aged 10 months), 6 cases of Alzheimer-type dementia (ATD) and 19 control subjects (13 aged 40-88 years and 6 aged 9-18 months). Neurotensin concentrations in anterior and basal hypothalamus, amygdala, septal area, caudate nucleus and temporal cortex were unaltered in ATD. The concentrations of neurotensin were significantly increased in the caudate nucleus, temporal cortex and frontal cortex in the cases of Down's syndrome aged 53-63 years with the neuropathological features of ATD, and were also increased in the cerebral cortex of the 27-year-old, which did not have the neuropathological features of ATD, and in two infant Down's cases. ChAT activity was reduced in the ATD and the 53-63-year-old cases of Down's syndrome, but not in the 27-year or 10-month-old Down's cases. The increased neurotensin concentrations appear to be a feature of Down's syndrome not related to the presence of plaques and neurofibrillary tangles or to a deficit in ChAT activity.

Timm's method modified for human tissue and compatible with adjacent section histofluorescence in the rat.

A simple dip method of Timm staining was developed. Because perfusion with sulphides and/or aldehydes is not required for adequate staining, the method can be employed with more control on human tissue taken at autopsy. Timm-stained human hippocampus reveals silver deposition in the mossy fiber region with a distribution similar to that in rats, but with some variation in the extent of penetration into stratum pyramidale. Adjacent cryostat sections of rat brain can be reacted for glyoxylic acid induced fluorescence by using the SPG dip method.

Cerebral cortex and amino acid neurotransmitters: higher levels of aspartic acid but not GABA in the frontal cortex of the rat.

Endogenous levels of Aspartic acid, GABA and Glutamic acid plus Glutamine were measured in the frontal, occipital, temporal and parietal cortex. Aspartic acid levels were found higher in the frontal cortex than in the rest of the cortical areas studied. GABA, however, had a homogenous distribution among all cortical areas.