A Brain Regional Analysis of Morphologic and Cholinergic Abnormalities in Alzheimer's Disease

Gs, Zubenko; Moossy, John; Aj, Martínez; Gr, Rao; Kopp, Ursula; Hanin, Israel

doi:10.1001/archneur.1989.00520420054022

Cited by 53 publications

(25 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is also in line with the known distribution of neuropathological changes (Mann et al, 1985;Katzman et al, 1988). As found previously MRB was in general unchanged (Perry et al, 1978;Gottfries et al, 1983;Zubenko et al, 1989) indicating sparing of muscarinic receptors in AD. Although some loss of MRB can be found in most severely demented younger AD patients (Reinikainen et al, 1987b), probably due to the loss of presynaptic muscarinic receptors (Mash et al, 1985), the muscarinic postsynaptic cholinergic receptors are not clearly affected in AD thus leaving possibilities for cholinergic replacement therapy, The present study also demonstrated significant reductions in the concentrations of 5HT, SHTAA, NA and DA in the cerebral cortex, hippocampus and striatum in AD patients.…”

Section: Discussionsupporting

confidence: 89%

Neurotransmitter changes in alzheimer's disease: Implications to diagnostics and therapy

Reinikainen

Soininen²,

Riekkinen³

1990

J of Neuroscience Research

213

106

View full text Add to dashboard Cite

Changes in the cholinergic, serotonergic, noradrenergic, dopaminergic, GABAergic and somatostatinergic neurons were investigated to determine their roles in Alzheimer's disease (AD). Markers for these systems were analyzed in postmortem brain samples from 20 patients with AD and 14 controls. In the CSF study, markers for the cholinergic neurons (choline esterase, ChE) and for the somatostatinergic neurons (somatostatin-like immunoreactivity, SLI) were assayed for 93 and 75 probable AD patients and 29 and 19 controls, respectively. Activity of choline acetyltransferase (CAT) was decreased by 50-85% in four cortical areas and hippocampus in patients with AD, but not in other areas of the brain, indicating a profound deficit in the function of cholinergic projections ascending from the nucleus basalis to the cerebral cortex and hippocampus in AD. Muscarinic receptor binding was reduced by 18% in the frontal cortex but not in other areas of the brain in AD. Serotonin (5HT) concentrations were reduced (by 21-37%) in hippocampal cortex, hippocampus and striatum; and 5HT metabolite levels were lowered (by 39-54%) in three cortical areas, thalamus and putamen in AD patients. Concentrations of noradrenaline (NA) were reduced (18-36%) in frontal and temporal cortex and putamen. These data imply that serotonergic and noradrenergic projections are also affected in AD but less than the cholinergic neurons. Dopamine (DA) concentrations in AD patients were reduced by 18-27% in temporal and hippocampal cortex and hippocampus, while HVA, the metabolite of DA, was unaltered. Glutamic acid decarboxylase activity was not altered in AD. SLI was decreased (28-42%) in frontal, temporal and parietal cortex, but not in thalamus and putamen in patients with AD. Frontal tangle scores correlated most strongly with cortical CAT activity reduction and less so with decreases of 5HT, NA and DA, indicating a closer correlation with the cholinergic changes and severity of AD than with other neurotransmitter deficiencies. ChE activity and SLI were reduced by 20% and 35%, respectively, in CSF of the whole group of AD patients as compared to the controls. Comparison of CSF findings between four subgroups of dementia severity indicated that the SLI was already reduced in the group of mildest AD (-31%), while ChE activity was not. Although ChE activity in CSF declined in relation to dementia severity, however, the maximal reduction was only modest (-30%). On the other hand, SLI in CSF showed only a slight further reduction (up to -41%) as the dementia become more severe.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

Section: Discussionsupporting

confidence: 89%

Neurotransmitter changes in alzheimer's disease: Implications to diagnostics and therapy

Reinikainen

Soininen²,

Riekkinen³

1990

J of Neuroscience Research

213

106

View full text Add to dashboard Cite

show abstract

“…When comparing the two subgroups (Table 4), biparietal and left temporo-occipital perfusion ratios were significantly lower when the age of onset of the dementia was earlier than 65 years. This is consistent with histopathological or biochemical studies that demonstrated more severe abnormalities in the pre-senile form of dementia when compared with the senile form (Wilcock and Esiri 1983;Bowen et al 1982;Yates et al 1983;Zubenco et al 1989). Nevertheless, dementia duration was significantly different between the two subgroups (Table 2), and, moreover, it was negatively correlated with MMS score as well as with left parieto temporal hypoperfusion within the whole group.…”

Section: Dementia Of the Alzheimer's Typesupporting

confidence: 86%

A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia

et al. 1991

View full text Add to dashboard Cite

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPET) using technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) as a tracer, in 13 control subjects and 44 age-matched patients suffering from dementia of the Alzheimer's type (DAT, n = 19), presumed Pick's disease (n = 5), idiopathic Parkinson's disease with dementia (DPD, n = 15) and progressive supranuclear palsy (PSP, n = 5). HMPAO uptake was measured in the superior frontal, inferior frontal, parietal, temporal and occipital cortices, and the perfusion values were expressed as cortical/cerebellar activity ratios. As compared with controls, tracer uptake ratios in the DAT group were significantly reduced over all cortical regions, with the largest defects in the parieto-temporal and superior frontal cortices. A marked hypoperfusion affecting the superior and inferior frontal cortices was found in Pick's disease, whereas a mild but significant hypoperfusion was observed only in the superior frontal cortex of patients with PSP. In the DPD group, HMPAO uptake was significantly reduced in the parietal, temporal and occipital cortices, but not in the frontal cortex. These results show that DAT and DPD share an opposite anteroposterior HMPAO uptake defect as compared with the Pick's and PSP groups.

show abstract

“…Hence it has been suggested that elevation of the acetylcholine (ACh) level might be helpful in attempts to improve the symptoms of cognitive deficits in AD [15] . Loss of cholinergic innervation, as demonstrated by reduced choline acetyltransferase (ChAT) and elevated acetylcholinesterase (AChE) activity is well correlated with the degree of dementia and severity of the neuropathological hallmarks of AD [16,17] . Therefore, NAR through its inhibitory effect on acetylcholinesterase activity could exert a mitigating effect on amnesia in experimental model of SAD.…”

Section: Discussionmentioning

confidence: 99%

Effect of Naringenin on Intracerebroventricular Streptozotocin-Induced Cognitive Deficits in Rat: A Behavioral Analysis

Baluchnejadmojarad

Roghani²

2006

Pharmacology

View full text Add to dashboard Cite

Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. The beneficial effect of naringenin (NAR) was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg). The STZ-injected rats received NAR (50 mg/kg/day p.o.) starting 1 day pre-surgery for 3 weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM) task was used. It was found out that NAR-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, NAR administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test. Therefore, these results demonstrate the effectiveness of NAR in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer’s disease.

show abstract

A Brain Regional Analysis of Morphologic and Cholinergic Abnormalities in Alzheimer's Disease

Cited by 53 publications

References 30 publications

Neurotransmitter changes in alzheimer's disease: Implications to diagnostics and therapy

Neurotransmitter changes in alzheimer's disease: Implications to diagnostics and therapy

A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia

Effect of Naringenin on Intracerebroventricular Streptozotocin-Induced Cognitive Deficits in Rat: A Behavioral Analysis

Contact Info

Product

Resources

About