Hans Förstl

Decreased phospholipase A2 activity in Alzheimer brains

Phospholipase A2 (PLA2) is a key-enzyme in the metabolism of membrane phospholipids. In cholinergic neurons PLA2 controls the physico-chemical properties of neuronal membranes as well as the breakdown of phosphatidylcholine to produce choline for acetylcholine synthesis. Moreover PLA2 influences the processing and secretion of the amyloid precursor protein, which gives rise to the beta-amyloid peptide, the major component of the amyloid plaque in Alzheimers disease (AD). In the present study PLA2 activity was investigated in post-mortem brains from 23 patients with AD and 20 nondemented elderly controls. In AD brains PLA2 activity was significantly decreased in the parietal and to a lesser degree in the frontal cortex. Lower PLA2 activity correlated significantly with an earlier onset of the disease, higher counts of neurofibrillary tangles and senile plaques and an earlier age at death, indicating a relationship between abnormally low PLA2 activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA2 activity may contribute to the cholinergic deficit and to the production of amyloidogenic peptides in the disease.

Decreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer's disease

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of membrane phospholipids. PLA2 influences the processing and secretion of the amyloid precursor protein, which give rise to the β-amyloid peptide, the major component of the amyloid plaque in Alzheimers disease (AD). We investigated the PLA2 activity in two samples: in post-mortem brains from 23 patients with AD and 20 non-demented elderly controls, and platelets from 16 patients with a diagnosis of probable AD, 13 healthy controls and 14 elderly patients with a major depression. In AD brains PLA2 activity was significantly decreased in the parietal, and to a lesser degree in the frontal, cortex. Lower PLA2 activity correlated significantly with an earlier onset of the disease, an earlier age at death and higher counts of neurofibrillary tangles and senile plaques. In platelets PLA2 activity was also significantly reduced in the AD group as compared with healthy and depressed controls. The reduction of the enzyme activity in platelets correlated with an early disease onset and with the severity of cognitive impairment, indicating a relationship between abnormally low PLA2 activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA2 activity may contribute to the production of amyloidogenic peptides in the disease. Further studies are needed to examine whether PLA2 activity in platelets may be useful as a peripheral marker for a subgroup of patients with AD.

Apolipoprotein E-4 gene dose in clinically diagnosed Alzheimer's disease: prevalence, plasma cholesterol levels and cerebrovascular change

SummaryThe prevalence of the apolipoprotein E-4 allele (ApoE-4) was significantly higher in a referral population of 40 patients with clinically diagnosed Alzheimers disease than in a sample of non-demented elderly controls (P<0.01). The highest plasma cholesterol levels were found in demented patients homozygotic for Apo E-4, but no significant increases of glucose, triglycerides and thyroxine or of leuko-araiosis and brain infarcts were verified in this preliminary study.

World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of dementias in primary care.

Abstract Objective. To define a practice guideline for biological treatment of dementias for general practitioners in primary care. Methods. TThis paper is a short and practical summary of the World Federation of Biological Psychiatry (WFSBP) guidelines for the Biological treatment of Alzheimers disease and other dementias for treatment in primary care (Ihl et al. 2011). The recommendations were developed by a task force of international experts in the field and are based on randomized controlled studies. Results. Anti-dementia medications neither cure, nor arrest, or alter the course of the disease. The type of dementia, the individual symptom constellation and the tolerability and evidence for efficacy should determine what medications should be used. In treating neuropsychiatric symptoms, psychosocial intervention should be the treatment of first choice. For neuropsychiatric symptoms, medications should only be considered when psychosocial interventions are not adequate and after cautious risk-benefit analysis. Conclusions. Depending on the diagnostic entity and clinical presentation different anti-dementia drugs can be recommended. These guidelines provide a practical approach for general practitioners managing dementias.