de Las Cuevas N, Urcelay E, Hermida OG, Saíz-Diaz RA, Bermejo F, Ayuso MS, Martín-Requero A. Ca2+/calmodulin-dependent modulation of cell cycle elements pRb and p27kip1 involved in the enhanced proliferation of lymphoblasts from patients with Alzheimer dementia. Neurobiol Dis. 2003 Aug;13(3):254-63. PubMed.
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Banner Research Institute
Studies of lymphocytes in AD make a frequent appearance in the literature. Papers have been published that describe effects of AD on lymphocytic apoptosis, telomere length, calcium (e.g., Sulger et al., 1999; Palotas et al., 2002), CD45, oxidative damage cell cycle (e.g., Stieler et al., 2001; Nagy et al., 2002) and defective calcium signaling (see Mattson et al., 2001, for review). Investigation of PS1 transgenic mice have also shown selected effects on lymphocytes, including in reactive oxygen species and calcium.
So what does the current manuscript add to the picture? For one, it provides additional information concerning potential mechanisms by which AD may affect cell cycle-related genes in AD. It would be of interest to see whether examination of primary lymphocytes, rather than immortalized cells, might confirm these results. In addition, it will be interesting to see the data in more detail, particularly with respect to the degree of overlap between AD and control data. This is especially pertinent since univariate studies to date have shown considerable overlap between AD and control samples, a finding with multiple potential implications. Other questions include whether the effects seen may be specific to AD or represent general markers of a neurodegenerative disease (less probable, in my opinion). But perhaps more importantly, the present study constitutes one more addition to the weight of evidence that AD is a systemic disease with important brain manifestations. Whether the systemic or the brain components of disease are cause or effect remains an open question. Also open is the definition of the link between events described in blood cells in AD and events in brain.
References:
Sulger J, Dumais-Huber C, Zerfass R, Henn FA, Aldenhoff JB. The calcium response of human T lymphocytes is decreased in aging but increased in Alzheimer's dementia. Biol Psychiatry. 1999 Mar 15;45(6):737-42. PubMed.
Palotás A, Kálmán J, Palotás M, Juhász A, Janka Z, Penke B. Fibroblasts and lymphocytes from Alzheimer patients are resistant to beta-amyloid-induced increase in the intracellular calcium concentration. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Jun;26(5):971-4. PubMed.
Stieler JT, Lederer C, Brückner MK, Wolf H, Holzer M, Gertz HJ, Arendt T. Impairment of mitogenic activation of peripheral blood lymphocytes in Alzheimer's disease. Neuroreport. 2001 Dec 21;12(18):3969-72. PubMed.
Nagy Z, Combrinck M, Budge M, McShane R. Cell cycle kinesis in lymphocytes in the diagnosis of Alzheimer's disease. Neurosci Lett. 2002 Jan 11;317(2):81-4. PubMed.
Mattson MP, Chan SL, Camandola S. Presenilin mutations and calcium signaling defects in the nervous and immune systems. Bioessays. 2001 Aug;23(8):733-44. PubMed.
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