The common marmoset as a model of neurodegeneration

Bridging the rodent to human translational gap: Marmosets as model systems for the study of Alzheimer's disease

“…It is important to note that marmosets manifest age‐related changes in a spectrum of functional and physiological parameters that mirror those in aging humans, including decreases in lean body mass, reduced serum albumin, increased insulin resistance, decreased hippocampal neurogenesis, cognitive impairment, myocardial fibrosis, and age‐related AD co‐morbidities including cancer, diabetes, and chronic renal disease 15–17 . Of particular relevance as a potential model for AD and similar to other primate species, the sequence homology of Aβ in marmosets is identical to that of humans, with the natural, sporadic presentation of Aβ in marmoset brain that occurs with aging 16–24 . Interestingly, although the sporadic presentation of amyloid plaques has been reported as early as 7 years in normal aging marmosets, experimental studies including Aβ‐seeding approaches report an accelerated progression of Aβ deposition as early as 5 years, with a similar spatial‐temporal pattern of Aβ deposition to that of humans and similarly with diverse presentation across individuals 21,24 .…”

“…Furthermore, cerebral amyloid angiopathy (CAA) has also been reported in aging marmosets, which is another important feature of AD that is not observed naturally in rodent models 24 . In addition, the amino acid sequence alignment of tau in marmoset has improved homology over mice, with 94.3% alignment to humans (vs 88.2% mouse to human) 17,22–23 . Only a few studies to date have investigated the presence of neurofibrillary tau tangles and neurodegeneration, which are prominent features of human AD, with several reports providing evidence of abnormal tau phosphorylation in aged NHP brains, including that of marmosets 21–24 .…”

“…Of interest, sex differences have also been reported with cognitive impairment in aging marmosets, with worse outcomes in aging females relative to aging males both in task performance and functional connectivity measures 30,31 . Other highly translational features of marmosets include the anatomic similarity of the marmoset cochlea to that of humans, which is relevant for studies of age‐related hearing loss 16–17,32–34 . Marmosets have color vision similar to humans, with male marmosets reported as di‐chromatic.…”

“…This short lifespan allows longitudinal studies in the same individuals over a reasonable period. It is important to note that marmosets manifest age‐related changes in a spectrum of functional and physiological parameters that mirror those in aging humans, including decreases in lean body mass, reduced serum albumin, increased insulin resistance, decreased hippocampal neurogenesis, cognitive impairment, myocardial fibrosis, and age‐related AD co‐morbidities including cancer, diabetes, and chronic renal disease 15–17 . Of particular relevance as a potential model for AD and similar to other primate species, the sequence homology of Aβ in marmosets is identical to that of humans, with the natural, sporadic presentation of Aβ in marmoset brain that occurs with aging 16–24 .…”

“…Relatedly, marmosets are excellent at performing cognitive tasks across several domains, including learning, memory, and attention. In addition, marmosets demonstrate age‐dependent cognitive decline with impairments associated with synaptic loss and reduced spine density 16–17,25–31 . Of interest, sex differences have also been reported with cognitive impairment in aging marmosets, with worse outcomes in aging females relative to aging males both in task performance and functional connectivity measures 30,31 .…”