Elevated levels of fragmented DNA nucleosomes in native and activated lymphocytes indicate an enhanced sensitivity to apoptosis in sporadic Alzheimer's disease. Specific differences to vascular dementia.

Apoptotic cell death is thought to be the most likely mechanism of cell death contributing to neurodegeneration in Alzheimer's disease (AD). Here, we provide evidence that in sporadic AD cases the vulnerability of peripheral cells to undergo apoptosis is increased compared to non-demented elderly controls and, very importantly, to patients with subcortical vascular encephalopathy (SVE) as another, but demented control group. Quiescent 'native' and 'activated' lymphocytes from AD patients that were predisposed to commit apoptotic cell death by priming the cells with interleukin-2, are shown to accumulate apoptosing cells to a significantly higher extent in spontaneous and in oxidative stress-induced in vitro apoptosis.

The calcium response of human T lymphocytes is decreased in aging but increased in Alzheimer's dementia.

Background: A significant increase in the [Ca2+]i response of single T lymphocytes to mitogenic stimulation with phytohemagglutinin is reported for 27 Alzheimer patients compared with 27 healthy gender- and age-matched control subjects, regardless of gender.

Methods: The [Ca2+]i signals of T lymphocytes were assessed using the Fura-2-AM method.

Results: In Alzheimer's disease (AD) the reaction pattern is similar to that seen in a group of 27 young healthy control subjects who exhibited a marked [Ca2+]i rise after stimulation.

Lymphocytes as cell model to study apoptosis in Alzheimer's disease: vulnerability to programmed cell death appears to be altered.

Recent evidence indicates that programmed cell death (apoptosis) may contribute to neuronal death in Alzheimer's disease (AD). In situ data derived from post mortem brain tissue indicate that DNA fragmentation which represents an important and typical apoptotic feature is markedly increased in brain cells of AD patients compared to controls. Furthermore, in vitro studies demonstrate that the peptide beta-amyloid (A beta) and its fragments induce apoptosis in neuronal cell cultures.

Changes of intracellular calcium regulation in Alzheimer's disease and vascular dementia.

Free intracellular calcium ([Ca2+]i) represents probably the most important intracellular messenger for many signal transduction pathways. Due to this crucial role of [Ca2+]i, it has been assumed that alterations of [Ca2+]i are critically involved in brain aging and in the pathophysiology of Alzheimer's disease (AD). This hypothesis is corroborated by several studies demonstrating changes of [Ca2+]i in peripheral cells from AD patients.

Enhanced vulnerability to apoptotic cell death in sporadic Alzheimer's disease.

All important neuropathological features like neurodegeneration and amyloid deposition occur similarly in familial and in sporadic Alzheimer's disease (AD) patients, suggesting a common pathogenetic mechanism. We investigated whether defective vulnerabilty to the induction of the apoptotic cell death pathway might be one of the underlying mechanisms leading to progressive cell death in sporadic AD. Our test could prove useful in supporting the diagnosis of AD and in predicting individuals predisposed to AD.