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Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, Couillard-Després S, Aigner L, Li G, Peskind ER, Kaye JA, Quinn JF, Galasko DR, Xie XS, Rando TA, Wyss-Coray T. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011 Sep 1;477(7362):90-4. PubMed.
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Just an observation: My 86-year-old father with Alzheimer's onset in 2006 had a gastrointestinal bleed and received 11 units of packed cells. After the first six units, his short-term memory improved significantly. He was able to read news articles and explain them 30 minutes later. Remembered visitors and their conversations. Did not repeat himself or ask the same questions repeatedly. Now at three weeks out from the last transfusion and no active bleeding, the short-term memory has returned to baseline, i.e., very poor. Coincidence, maybe, but it was nice to have "real" Dad back for a while.
View all comments by Carol DelanyI'd like to see an ARF Webinar on this topic.
View all comments by J. Lucy Boydretired
Eotaxin or CCL 11 is known to recruit eosinophiles. This is thought to indicate a relationship to allergic reactions. Eosinophilic bodies have been reported in Alzheimer's disease cortex on neuropathological exams. They have been described as homogeneous electron-dense bodies on electron microscopic examination (1).
Possibly, there is some type of allergic response, or eosinophiles are being recruited by CCL 11 with resulting adverse effects on the brain and the brain deterioration noted in Alzheimer's disease.
References:
Inoue M, Yagishita S, Itoh Y, Koyano S, Amano N, Matsushita M. Eosinophilic bodies in the cerebral cortex of Alzheimer's disease cases. Acta Neuropathol. 1996 Dec;92(6):555-61. PubMed.
View all comments by Steven BrennerUniversity of Wisconsin
This paper supports the reproductive-cell cycle theory of aging, which indicates that reproductive endocrine dyscrasia mediates aging in all tissues via altered cell cycle signaling (Bowen and Atwood, 2004; Atwood and Bowen, 2011). The blood-borne factors inducing brain aging may, in fact, be due to elevated concentrations of circulating gonadotropins and GnRH, and decreased concentrations of sex steroids and inhibin, in the aged post-reproductive mouse. This work is further supported by the finding that transplantation of young ovaries (two-month-old) into middle-aged (11-month-old) mice significantly increased longevity by re-establishing the hypothalamic-pituitary-gonadal axis. These data indicate that reproductive hormones are primarily responsible for aging. Supporting this, the major cytokines correlated with aging in the 2011 paper by Villeda et al.—CCL2, haptoglobulin, and eotaxin (CCL11)—are regulated by (Bouckaert et al., 1986; Dahm-Kähler et al., 2006), or correlated with (Kass et al., 2010) LH and FSH concentrations.
References:
Bowen RL, Atwood CS. Living and dying for sex. A theory of aging based on the modulation of cell cycle signaling by reproductive hormones. Gerontology. 2004 Sep-Oct;50(5):265-90. PubMed.
Atwood CS, Bowen RL. The reproductive-cell cycle theory of aging: an update. Exp Gerontol. 2011 Feb-Mar;46(2-3):100-7. PubMed.
Bouckaert PX, Evers JL, Doesburg WH, Schellekens LA, Brombacher PH, Rolland R. Patterns of changes in proteins in the peritoneal fluid of women during the periovulatory phase of the menstrual cycle. J Reprod Fertil. 1986 Jul;77(2):329-36. PubMed.
Dahm-Kähler P, Runesson E, Lind AK, Brännström M. Monocyte chemotactic protein-1 in the follicle of the menstrual and IVF cycle. Mol Hum Reprod. 2006 Jan;12(1):1-6. PubMed.
Kåss AS, Lea TE, Torjesen PA, Gulseth HC, Førre ØT. The association of luteinizing hormone and follicle-stimulating hormone with cytokines and markers of disease activity in rheumatoid arthritis: a case-control study. Scand J Rheumatol. 2010 Mar;39(2):109-17. PubMed.
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