Leslie Iversen

Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer type.

Post-mortem brain tissue from 15 patients dying with a diagnosis of senile dementia of Alzheimer type (SDAT) was compared with tissue obtained from 16 control patients at routine post-mortem. A significant fall in choline acetyltransferase (ChAT) activity was observed in the cortex, hippocampus and amygdala of the SDAT cases and was maximal in the temporal cortex. The fall in ChAT activity observed in the temporal cortex was accompanied by a significant reduction (47%) in immunoreactive somatostatin.

The substantia innominata in Alzheimer's disease: an histochemical and biochemical study of cholinergic marker enzymes.

Acetylcholinesterase staining was examined in the substantia innominata of 3 normal human brains. Large intensely stained neurones were seen within the region of the basal nucleus of Meynert which is believed to be the origin of the cholinergic projection to the neocortex in animals. On the basis of the acetylcholinesterase staining pattern, the substantia innominata was dissected from post-mortem brain tissue of 19 cases of Alzheimers disease (AD) and 16 controls so as to include the basal nucleus. Choline acetyltransferase (ChAT) activity was found to be reduced in the substantia innominata and amygdala in AD but not in the adjacent lentiform nucleus and hypothalamus.

Reduced corticol choline acetyltransferase activity in senile dementia of Alzheimer type is not accompanied by changes in vasoactive intestinal polypeptide

Post-mortem brain tissue from 7 patients who died with a diagnosis of senile dementia of Alzheimer type (SDAT) was compared with tissue obtained from 7 control patients at routine post mortem. A significant fall in choline acetyltransferase (ChAT) activity was apparent in the cerebral cortex of the SDAT cases which was maximal in the temporal lobe. The fall in ChAT activity was not accompanied by changes in cortical vasoactive intestinal polypeptide (VIP) measured by radioimmunoassay.

EXTRAHYPOTHALAMIC VASOPRESSIN IN HUMAN-BRAIN

The distribution of arginine vasopressin immunoreactivity in post-mortem human brain was examined using a radioimmunoassay. The highest concentration was found in the hypothalamus but substantial amounts of vasopressin-like immunoreactivity were also found in the locus coeruleus, periaqueductal grey, substantia nigra compacta and reticulata and in lower concentrations in the globus pallidus. The extrahypothalamic vasopressin was immunologically and chromatographically similar to hypothalamic vasopressin. The possibility arises that the high levels of vasopressin in the locus coeruleus may relate to an effect on noradrenergic transmission.

ARGININE VASOPRESSIN AND CHOLINE ACETYLTRANSFERASE IN BRAINS OF PATIENTS WITH ALZHEIMER TYPE SENILE DEMENTIA

or MHPG. The incidence of Alzheimer type changes in Down patients under the age of 40 is less than 2% and this increases dramatically to 100% past this age.4 Therefore, although neuropathological confirmation is lacking, it can be presumed that plaques and tangles would both be abundant in our older group of Down’s patients and would most likely be absent in the younger group, since the groups clearly fall on either side of the 40 years of age threshold which marks4 the onset of these pathological features within brains of older patients. It appears, therefore, that development of Alzheimer type lesions in older patients with Down syndrome is not accompanied by changes in the brain’s noradrenaline system, as demonstrated by MHPG findings, nor does there seem to be a worsening of HVA in the older groups, as might be inferred from an additional cholinergic involvement at that age. The changes in HVA we found in the younger Down group may represent an abnormality of development which persists into later life and is not further aggravated by the acquisition of Alzheimer type lesions. The cholinergic alterations in older Down patients reported by Yates et al. may therefore be likewise related to developmental deficiencies at an earlier age, which would still be apparent in the middle-aged patients investi. gated by them. Clearly, there is need for a full histological and biochemical appraisal of both aminergic and cholinergic neurones, in both young and old Down patients, before the significance of acquisition of Alzheimer type lesions in this condition can be ascertained.

Extrahypothalamic vasopressin is unchanged in Parkinson's disease and Huntington's disease

Vasopressin immunoreactivity was measured post-mortem in the locus coeruleus and substantia nigra of 16 cases of Parkinsons disease and multisystem atrophy, 10 cases of Huntingtons chorea and 28 normal controls. Amounts of vasopressin did not differ significantly (P greater than 0.05) between the 3 groups. Immunohistochemistry demonstrated vasopressin within nerve terminals. These data are consistent with an extrinsic vasopressin system in the human locus coeruleus and substantia nigra.

Benzodiazepine receptors: The effect of GABA on their characteristics in human brain and their alteration in Huntington's disease

The characteristics of bezodiazepine (BDZ) receptors were studied in the putamen and substantia nigra (SN) of control and Huntingtons disease (HD) human brains. In the putamen, there was a significant decrease in density BDZ receptors in the HD tissue. In addition the application of GABA significantly potentiated DBZ receptor binding in both the HD and control putamen. In the SN, an increase in BDZ receptor density was detected in the HD tissue. GABA enhanced [3H]flunitrazepam binding in both the HD and control SN by increasing the affinity of BDZ receptors for [3H]flunitrazepam. The results suggest that there are alterations in BDZ receptors in HD human brain and that these alterations may be related to the neuronal pathology of this disease. This study also provides evidence for a coupling of GABA receptors to BDZ receptors in human brain.