Commentary: is Alzheimer's disease uniquely human?

Finch, Caleb E.; Austad, Steven N.

doi:10.1016/j.neurobiolaging.2014.10.025

Cited by 60 publications

(61 citation statements)

References 35 publications

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“…45,77,78 Decline in cognitive function in aging humans ranges from mild forgetfulness and slower data processing to severe dementia. Dementia is a syndrome in which thinking skills are impaired to the point that the individual can no longer perform daily functions.…”

Section: Nervous System Disordersmentioning

confidence: 99%

“…[87][88][89]135,193,206 Other hallmarks, such as dystrophic neurites and tau-neurofibrillary tangles, are less common, leading some authors to believe that true Alzheimer disease is likely unique to the human ape. 77 In orangutans (28, 31, and 36 yo), low numbers of amyloid plaques were Figure 7. Mild hepatocellular anisokaryosis (polyploidy), multinucleation, and lipofuscinosis; liver, 48-year-old female chimpanzee.…”

Section: Nervous System Disordersmentioning

confidence: 99%

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Comparative Pathology of Aging Great Apes

2015

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The great apes (chimpanzees, bonobos, gorillas, and orangutans) are our closest relatives. Despite the many similarities, there are significant differences in aging among apes, including the human ape. Common to all are dental attrition, periodontitis, tooth loss, osteopenia, and arthritis, although gout is uniquely human and spondyloarthropathy is more prevalent in apes than humans. Humans are more prone to frailty, sarcopenia, osteoporosis, longevity past reproductive senescence, loss of brain volume, and Alzheimer dementia. Cerebral vascular disease occurs in both humans and apes. Cardiovascular disease mortality increases in aging humans and apes, but coronary atherosclerosis is the most significant type in humans. In captive apes, idiopathic myocardial fibrosis and cardiomyopathy predominate, with arteriosclerosis of intramural coronary arteries. Similar cardiac lesions are occasionally seen in wild apes. Vascular changes in heart and kidneys and aortic dissections in gorillas and bonobos suggest that hypertension may be involved in pathogenesis. Chronic kidney disease is common in elderly humans and some aging apes and is linked with cardiovascular disease in orangutans. Neoplasms common to aging humans and apes include uterine leiomyomas in chimpanzees, but other tumors of elderly humans, such as breast, prostate, lung, and colorectal cancers, are uncommon in apes. Among the apes, chimpanzees have been best studied in laboratory settings, and more comparative research is needed into the pathology of geriatric zoo-housed and wild apes. Increasing longevity of humans and apes makes understanding aging processes and diseases imperative for optimizing quality of life in all the ape species.

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Section: Nervous System Disordersmentioning

confidence: 99%

Section: Nervous System Disordersmentioning

confidence: 99%

Comparative Pathology of Aging Great Apes

2015

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“…Transgenic rodent models overproducing human-sequence Aβ develop profuse senile plaques and cerebral amyloid-β angiopathy (CAA), but they do not have substantial, AD-like neuronal cell loss, neurofibrillary tangles, and/or profound memory impairment (Jucker, 2010,Morrissette, et al, 2009). Aged nonhuman primates naturally accumulate abundant multimeric, human-sequence Aβ in plaques and CAA (D'Angelo, et al, 2013,Elfenbein, et al, 2007,Gearing, et al, 1996,Gearing, et al, 1997,Geula, et al, 2002,Heuer, et al, 2012,Lemere, et al, 2004,Lemere, et al, 2008,Perez, et al, 2013,Selkoe, et al, 1987,Walker, et al, 1990), yet they appear to be resistant to other behavioral and pathologic features that define AD in humans (Finch and Austad, 2012,Finch and Austad, 2015,Heuer, et al, 2012,Walker and Cork, 1999). Similarly, dogs generate human-sequence Aβ and manifest senile plaques and CAA in old age, but they also do not exhibit all features of AD (Fast, et al, 2013,Head, 2013).…”

Section: Introductionmentioning

confidence: 99%

Comparative pathobiology of β-amyloid and the unique susceptibility of humans to Alzheimer's disease

Rosen

Tomidokoro

Farberg

et al. 2016

Neurobiology of Aging

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The misfolding and accumulation of the protein fragment Aβ is an early and essential event in the pathogenesis of Alzheimer's disease (AD). Despite close biological similarities among primates, humans appear to be uniquely susceptible to the profound neurodegeneration and dementia that characterize AD, even though nonhuman primates deposit copious Aβ in senile plaques and cerebral amyloid-β angiopathy as they grow old. Since the amino acid sequence of Aβ is identical in all primates studied to date, we asked whether differences in the properties of aggregated Aβ might underlie the vulnerability of humans and the resistance of other primates to AD. In a comparison of aged squirrel monkeys (Saimiri sciureus) and humans with AD, immunochemical and mass spectrometric analyses indicate that the populations of Aβ fragments are largely similar in the two species. In addition, Aβ-rich brain extracts from the brains of aged squirrel monkeys and AD patients similarly seed the deposition of Aβ in a transgenic mouse model. However, the epitope exposure of aggregated Aβ differs in SDS-stable oligomeric Aβ from the two species. In addition, the high-affinity binding of 3H Pittsburgh Compound B (PiB) to Aβ is significantly diminished in tissue extracts from squirrel monkeys compared to AD patients. These findings support the hypothesis that differences in the pathobiology of aggregated Aβ among primates are linked to post-translational attributes of the misfolded protein, such as molecular conformation and/or the involvement of species-specific cofactors.

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“…For instance, late-onset Alzheimer's disease (LOAD) is considered to be unique to humans (7). In fact, whereas humans accumulate amyloid beta deposits and neurofibrillary tangles composed of hyperphosphorylated tau protein after age 40 y, postmortem brain samples from age-matched chimpanzees and other great apes do not show the complete pathology of LOAD (8)(9)(10). Human-unique neurodegenerative diseases could be byproducts of major differences in brain development that evolved along the human lineage.…”

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confidence: 99%

Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

Schwarz

Springer

Altheide

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer’s dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer’s disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin.

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Commentary: is Alzheimer's disease uniquely human?

Cited by 60 publications

References 35 publications

Comparative Pathology of Aging Great Apes

Comparative Pathology of Aging Great Apes

Comparative pathobiology of β-amyloid and the unique susceptibility of humans to Alzheimer's disease

Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

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