Colocalization of different types of amyloid in the walls of cerebral blood vessels of patients suffering from cerebral amyloid angiopathy and spontaneous intracranial hemorrhage: a report of 5 cases.

Four cases of spontaneous intracranial hemorrhage (ICH) are described in which the diagnosis of a cerebral amyloid angiopathy (CAA) was made in the biopsy specimens. In one further case CAA was detected on autopsy after intracranial hemorrhage (ICH). Amyloidotic degeneration of the vessel walls appeared to be the most likely reason for the ICH which in these cases especially involved superficial neocortical regions. In all cases, co-deposition of A4beta-amyloid and ALlambda-amyloid was found in diseased leptomeningeal and cortical vessels. Besides CAA, all 5 patients suffered from other diseases which had affected the blood vessel walls such as atherosclerosis, diabetes mellitus or arterial hypertension. However, no signs of systemic amyloidosis could be detected in these cases. It is suggested that the observed co-deposition of 2 amyloid subtypes is based on the combination of 2 different diseases, one of which results in a local production of A4beta-amyloid in the tunica media of cerebral blood vessels and another one, e.g. arterial hypertension, which impairs the permeability of the blood vessels by affection of the tunica intima allowing for the pathological penetration of circulating immunoglobulin lambda-light chains into the vessel wall. Subsequently, the preexisting A4beta-amyloid might have induced the polymerization of the lambda-light chains to ALlambda-amyloid in the media of the vessels and could have aggravated the amyloidotic degeneration of the vessel walls.

Reduced intraneuronal lipofuscin content in dementia with Lewy bodies compared with Alzheimer's disease and controls.

Lipofuscin has been of interest in dementia of Alzheimer's type (DAT), because of the hypothesis that dementia is a kind of premature ageing. The results of studies on intraneuronal lipofuscin content in DAT are inconsistent. At present no data on intraneuronal lipofuscin in dementia with Lewy bodies (DLB) are available. The amount of lipofuscin in the neurons of the inferior olivary nucleus of 10 brains of DLB patients, 10 of age-matched DAT patients, and 10 of age-matched controls has been measured microfluorometrically. The intraneuronal lipofuscin content in the DLB patients was significantly lower than in the DAT patients and controls. This finding may indicate a general alteration of neuronal cell metabolism in DLB, e.g. a defect of mitochondrial DNA, not confined to neurons developing Lewy bodies.

High proportion of dementia with Lewy bodies in the postmortems of a mental hospital in Germany.

OBJECTIVE: Dementia with Lewy bodies (DLB) is under-recognized in Germany. No data on the number of patients suffering from this condition in Germany are available at present. We were interested in the proportion of DLB in the postmortems of demented inpatients in the care of a psychogeriatric service. DESIGN: In a retrospective study we examined consecutive postmortems of inpatients who died in one mental hospital. SETTING: A suburban and rural old age psychiatry service in Germany. PATIENTS: 103 consecutive postmortems had been performed from 9/1987 to 6/1995. Fifty-nine (57.3%) of all cases warranted the clinical diagnosis of dementia (DSM-III-R). MEASURES: The causes of dementia were examined histologically. Lewy bodies (LBs) were detected with ubiquitin immunohistochemistry. RESULTS: DLB was the third most frequent cause of dementia (13.6% of demented), after dementia of Alzheimer's type (DAT) (35.6%) and mixed DAT and vascular dementia (15.3%), but ahead of 'pure' vascular dementia (MID). The DLB group showed a male preponderance compared with the DAT, MID and mixed group of our series. The DLB patients died younger than the DAT patients. The differences, however, were not statistically significant. All DLB cases showed neurofibrillary and amyloid pathology sufficient to warrant an additional diagnosis of DAT. Cases with 'pure' LB pathology had not been detected in our series. CONCLUSIONS: Our results indicate that by using appropriate methods, ie ubiquitin immunohistochemistry, a considerable number of DLB cases can be detected in postmortems of demented patients from German mental hospitals.

Accumulation of nuclear p53 protein and prognosis of astrocytomas in childhood and adolescence.

The aim of the study was to investigate whether nuclear immunopositivity for p53 is a factor of prognostic significance in astrocytomas of childhood and adolescence. Paraffin-embedded tissues of astrocytomas (10 WHO grade II, 11 WHO grade III) from 21 patients under 18 years of age, when operated for the first time, were studied immunohistochemically. We used a set of 6 different antibodies against p53, suitable for paraffin section (PAb1801, PAb240, DO-1, DO-7, BP53-12, CM-1). The intensity of the nuclear staining was scored and the percentage of stained nuclei counted. A tumor was scored positive if at least 10% of nuclei showed at least medium staining intensity with at least 1 primary antibody. No single antibody detected all cases designated immunopositive. This shows the advantage of using a set of antibodies. The time of survival in the immunopositive cases was significantly shorter, but immunopositivity was correlated with grade III (WHO). Comparing the time of survival between p53-immunopositive and -immunonegative grade III (WHO) astrocytomas no significant difference was found. We conclude that p53 immunoreactivity is not an independent unfavorable prognostic factor in astrocytomas of childhood and adolescence.

The lipofuscin content of nerve cells of the inferior olivary nucleus in Alzheimer's disease.

Lipofuscin, the age pigment, is of interest in Alzheimer's disease because of its property to accumulate in neurons and because of the hypothesis that Alzheimer's dementia is a kind of premature ageing. The amount of intraneuronal lipofuscin in the inferior olivary nucleus of 20 brains from patients with histologically confirmed Alzheimer's disease according to the CERAD protocol and of 20 controls has been measured microfluorometrically. Patients and controls were matched for age. The amount of lipofuscin in the neurons of the inferior olivary nucleus did not differ significantly between the cases of Alzheimer's disease and the controls. The result is discussed taking the findings of previous authors into account. We conclude that there is no evidence that lipofuscin plays an important role in the pathogenesis of Alzheimer's disease.