Alzheimer's Disease and Some Speculations about the Evolution of Its Modifiers

Sapolsky, Robert M.; Finch, Caleb E.

doi:10.1111/j.1749-6632.2000.tb05567.x

Cited by 15 publications

(11 citation statements)

References 16 publications

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“…Although motherly care is the norm in all mammal species, “grandmothering” in nonhuman primates is almost entirely unheard of. As Sapolsky and Finch note, this fits with the observation that dementia in nonhuman primates occurs shortly after reproductive senescence, whereas dementia in humans tends to occur around 20 years after menopause, allowing more time for postreproductive females to contribute to the care of their grandchildren [30]. …”

Section: Evolutionary Perspectives On the Genetics And Origins Of Adsupporting

confidence: 61%

“…Sapolsky and Finch discuss yet another way in which protective APOE alleles may be selected for: the human phenomenon of “grandmothering” [30]. Durable functioning in old age is selected for via kin selection [31]; that is, early humans who remained functionally able for longer were able to provide more care and food for their grandchildren, who in turn had a greater chance of survival and passing on those protective alleles to their own offspring.…”

Section: Evolutionary Perspectives On the Genetics And Origins Of Admentioning

confidence: 99%

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Some evolutionary perspectives on Alzheimer's disease pathogenesis and pathology

Glass

Arnold

2011

Alzheimer's & Dementia

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There is increasing urgency to develop effective prevention and treatment for Alzheimer's disease (AD) as the aging population swells. Yet, our understanding remains limited for the elemental pathophysiological mechanisms of AD dementia that may be causal, compensatory, or epiphenomenal. To this end, we consider AD and why it exists from the perspectives of natural selection, adaptation, genetic drift, and other evolutionary forces. We discuss the connection between the apolipoprotein E (APOE) allele and AD, with special consideration to APOE ε4 as the ancestral allele. The phylogeny of AD-like changes across species is also examined, and pathology and treatment implications of AD are discussed from the perspective of evolutionary medicine. In particular, amyloid-β (Aβ) neuritic plaques and paired helical filament tau (PHFtau) neurofibrillary tangles have been traditionally viewed as injurious pathologies to be targeted, but may be preservative or restorative processes that mitigate harmful neurodegenerative processes or may be epiphenoma of the essential processes that cause neurodegeneration. Thus, we raise fundamental questions about current strategies for AD prevention and therapeutics.

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Section: Evolutionary Perspectives On the Genetics And Origins Of Adsupporting

confidence: 61%

Section: Evolutionary Perspectives On the Genetics And Origins Of Admentioning

confidence: 99%

Some evolutionary perspectives on Alzheimer's disease pathogenesis and pathology

Glass

Arnold

2011

Alzheimer's & Dementia

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“…Nonetheless, the concept has been recently applied in attempts to explain Alzheimer's disease, prostate hyperplasia, and certain types of cancer [30]. Regarding Alzheimer's disease, a recently advanced evolutionary hypothesis [31,32] is built on findings of neuroprotective functions for estrogen and apolipoproteins E2 and E3. As estrogen declines in post-menopausal women, these apolipoproteins (uniquely evolved in humans) help delay the onset of Alzheimer's-like pathologies (and interestingly cardiovascular disease).…”

Section: Discussionmentioning

confidence: 99%

“…As estrogen declines in post-menopausal women, these apolipoproteins (uniquely evolved in humans) help delay the onset of Alzheimer's-like pathologies (and interestingly cardiovascular disease). With longevity increases over time in the human evolutionary lineage, older women having the neuroprotective apolipoproteins would have enjoyed a selective advantage since their ability to competently care for their grandchildren (with whom they share 1/4 of their DNA) was prolonged [31,32]. This special form of natural selection, in which a person gains a benefit by helping close relatives, is termed kin selection [1,33].…”

Section: Discussionmentioning

confidence: 99%

Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?

Harris

Malyango

2005

BMC Med Educ

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Background: Medical and pre-professional health students ask questions about human health that can be answered in two ways, by giving proximate and evolutionary explanations. Proximate explanations, most common in textbooks and classes, describe the immediate scientifically known biological mechanisms of anatomical characteristics or physiological processes. These explanations are necessary but insufficient. They can be complemented with evolutionary explanations that describe the evolutionary processes and principles that have resulted in human biology we study today. The main goal of the science of Darwinian Medicine is to investigate human disease, disorders, and medical complications from an evolutionary perspective.

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“…The activity of corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the hypothalamo-pituitary-adrenal (HPA) axis, which is increased at times of stress and in specific neurological and psychiatric disorders [1, 2]. Changes in the total number of CRH-expressing neurons in the PVN reflect the change in activity of CRH neurons [1,3,4,5], which was confirmed by in situ hybridization of CRH-mRNA, analyzed in the same patients [6,7,8].…”

Section: Introductionmentioning

confidence: 99%

Gender Difference in Age-Related Number of Corticotropin-Releasing Hormone-Expressing Neurons in the Human Hypothalamic Paraventricular Nucleus and the Role of Sex Hormones

Bao

Swaab²

2007

Neuroendocrinology

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Previous studies have shown that the total number of corticotropin-releasing hormone (CRH)-stained neurons in the human hypothalamic paraventricular nucleus (PVN) increases with age. To determine whether this age-related change depends on gender and whether circulating sex hormones play a role, we analyzed the total number of CRH-immunoreactive neurons by means of immunocytochemistry and image analysis in the postmortem hypothalamic PVN of 22 control subjects (11 males and 11 females) between the ages of 22 and 89 years, and of 10 subjects with abnormal sex hormone status. Our data show that men have a significantly larger number of CRH neurons than women (p = 0.004) and that the total number of CRH neurons increases significantly with age, but only in male controls (p = 0.032), not in female controls (p = 0.733). Female controls do not show a significant change in the total number of CRH neurons either before or after the age (50 years) of menopause (p = 0.792). Male subjects with low testosterone levels due to castration showed significantly fewer CRH neurons than well-matched intact males (p = 0.008), while castrated male-to-female (M-F) transsexuals with estrogen replacement showed normal numbers of CRH neurons. One male case, who had high estrogen levels due to an estrogen-producing tumor, showed a large number of CRH neurons. Thus, although circulating androgens and estrogens both seem to play a stimulatory role with respect to CRH neurons, the age-dependent increase in the number of CRH neurons in the PVN of men, which has been interpreted to reflect activation of the CRH neurons with age, seems to result from factors other than age-related changes of circulating sex hormone levels.

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Alzheimer's Disease and Some Speculations about the Evolution of Its Modifiers

Cited by 15 publications

References 16 publications

Some evolutionary perspectives on Alzheimer's disease pathogenesis and pathology

Some evolutionary perspectives on Alzheimer's disease pathogenesis and pathology

Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?

Gender Difference in Age-Related Number of Corticotropin-Releasing Hormone-Expressing Neurons in the Human Hypothalamic Paraventricular Nucleus and the Role of Sex Hormones

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