Old chimpanzees get Alzheimer’s pathology

Alzheimer’s Disease (AD) is the most common type of dementia with a progression that can span decades. Its prevalence is increasing steadily, particularly in the western countries and Australia. So some researchers speculated that this particular disease might be specific to humans. For various reasons, either genetic, social, or environmental.

A fresh e-pub brings new evidence that Alzheimer’s might plague other primates as well. Edler et al. (2017) studied the brains of 20 old chimpanzees (Pan troglodytes) for a whole slew of Alzheimer’s pathology markers. More specifically, they looked for these markers in brain regions commonly affected by AD, like the prefrontal cortex, the midtemporal gyrus, and the hippocampus.

Alzheimer’s markers, like Tau and Aβ lesions, were present in the chimpanzees in an age-dependent manner. In other words, the older the chimp, the more severe the pathology.

Interestingly, all 20 animals displayed some form of Alzheimer’s pathology. This finding points to another speculation in the field which is: dementia is just part of normal aging. Meaning we would all get it, eventually, if we would live long enough; some people age younger and some age older, as it were. This hypothesis, however, is not favored by most researchers not the least because is currently unfalsifiable. The longest living humans do not show signs of dementia so how long is long enough, exactly? But, as the authors suggest, “Aβ deposition may be part of the normal aging process in chimpanzees” (p. 24).

Unfortunately, “the chimpanzees in this study did not participate in formal behavioral or cognitive testing” (p. 6). So we cannot say if the animals had AD. They had the pathological markers, yes, but we don’t know if they exhibited the disease as is not uncommon to find these markers in humans who did not display any behavioral or cognitive symptoms (Driscoll et al., 2006). In other words, one might have tau deposits but no dementia symptoms. Hence the title of my post: “Old chimpanzees get Alzheimer’s pathology” and not “Old chimpanzees get Alzheimer’s Disease”

Good paper, good methods and stats. And very useful because “chimpanzees share 100% sequence homology and all six tau isoforms with humans” (p. 4), meaning we have now a closer to us model of the disease so we can study it more, even if primate research has taken significant blows these days due to some highly vocal but thoroughly misguided groups. Anyway, the more we know about AD the closer we are of getting rid of it, hopefully. And, soon enough, the aforementioned misguided groups shall have to face old age too with all its indignities and my guess is that in a couple of decades or so there will be fresh money poured into aging diseases research, primates be damned.

121-chimps get Alz - Copy

REFERENCE: Edler MK, Sherwood CC, Meindl RS, Hopkins WD, Ely JJ, Erwin JM, Mufson EJ, Hof PR, & Raghanti MA. (EPUB July 31, 2017). Aged chimpanzees exhibit pathologic hallmarks of Alzheimer’s disease. Neurobiology of Aging, PII: S0197-4580(17)30239-7, DOI: http://dx.doi.org/10.1016/j.neurobiolaging.2017.07.006. ABSTRACT  | Kent State University press release

By Neuronicus, 23 August 2017

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The FIRSTS: Betz pyramidal neurons (1874)

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Betz cell in the dog cortex. Copyright: RA Bergman, AK Afifi, PM Heidger, & MP D’Alessandro. Pic taken from here.

Bigger that Purkinje cerebellar neurons, the Betz pyramidal neurons (aka the giant pyramidal neurons) can have up to 100 micrometers in diameter. They are located in the fifth layer of the grey matter in the primary motor cortex. And they were discovered by a Ukrainian who did not receive the just place he deserves in the history of neuroscience, as most books on the subject ignore him. So let’s give him some attention.

Vladimir Alekseyevich Betz (1834–1894) was a professor of anatomy and a histologist at the Kiev University. Just like with Pavlov, sometimes there is nothing spectacular or weird or bizarre in the life of a great thinker. Betz was a child of a relatively wealthy family, went to good schools, then to Medical School, where he showed interest in the anatomy department. He continued his postgraduate studies in the West (that is Germany and Austria) after which he returned home where he got a position as a professor at his Alma Mater where he stayed until he died of heart problems at the age of 60.

Vladimir_Betz
Vladimir Alekseyevich Betz (1834 – 1894), License: PD

During his PhD, which was on the blood flow in the liver, Betz discovered an interest in histology. He was unsatisfied with the quality of the existing staining methods, so he worked for years to improve the fixation and staining methods of the brain tissue. His new methods allowed the cutting and preserving very thin slices and then he described what he saw. But Betz’s genius was in linking his cortical cytoarchitechtonic findings with physiological function, dividing the cortex into the motor and sensory areas. He also made revolutionary observations of the anatomical organization and development and various pathologies.

Original reference (which I did not find): Betz W (1874). Anatomischer Nachweis zweier Gehirncentra. Centralblatt für die medizinischen Wissenschaften. 12:578-580, 595-599.

Reference: Kushchayev SV, Moskalenko VF, Wiener PC, Tsymbaliuk VI, Cherkasov VG, Dzyavulska IV, Kovalchuk OI, Sonntag VK, Spetzler RF, & Preul MC (Jan 2012, Epub 10 Nov 2011). The discovery of the pyramidal neurons: Vladimir Betz and a new era of neuroscience. Brain, 135(Pt 1):285-300. doi: 10.1093/brain/awr276.  ArticleFREE FULLTEXT PDF

By Neuronicus, 17 December 2015

The FIRSTS: Adult neurogenesis (1962)

New neurons in the granular layer of the hippocampus. Fig. 30 from Altman & Das (1965).
New neurons in the granular layer of the hippocampus. Fig. 30 from Altman & Das (1965).

I am starting a new category today: the Firsts. It will feature articles that showed something really interesting for the first time. Yes, all articles show something for the first time, that’s why they are published. But I have noticed either a lack of acknowledgment (“it is known that x”) or a disregard for the old papers (“doesn’t count if it’s before, say, 2001”), particularly among the new generation of scientists. So I will feature both the really big ones (e.g., first proof of adult neurogenesis) or the more obscure, but nonetheless, first in their field (e.g., first synthesis of morphine).

Today, first proof of adult neurogenesis. Altman (1962) wanted to see the kinetics of glial proliferation after brain injury. Glial cells are the other type of cells in the brain and they outnumber the neurons 10 to 1. Altman lesioned the rat lateral geniculate nucleus (a portion of the thalamus that deals primarily with vision) and then injected the rats with thymidine-H3, a dye that labels the newly formed cells. In addition to the expected glial proliferation, he also observed (by microscope and careful histology) that some neurons were also stained with the dye, which means that they were born after the injection. The new neurons were in many regions of the brain (so not only those associated with the lesioned area), including the cortical areas.

Altman followed up and three years later published the first comprehensive study of postnatal (not adult) neurogenesis in dendate gyrus of the hippocampus.

References:

  1. Altman, J. (30 March 1962). Are New Neurons Formed in the Brains of Adult Mammals?. Science, 135 (3509): 1127-1128. DOI: 10.1126/science.135.3509.1127. Article | PDF
  2. Altman, J, & Das, G. D. (June 1965). Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. The Journal of Comparative Neurology, 124 (3): 319 –335. DOI: 10.1002/cne.901240303. Article | PDF

by Neuronicus, 30 September 2015

I’m not like you, inside and out

Credit: Dawn of the Planet of the Apes
Screenshot from “Dawn of the Planet of the Apes” (Director: Tim Burton, 2001)

One mistake than many neuroscientists make (myself included) is the implicit assumption that the human brain is a rodent brain scaled-up, plus a few more bits. Here is a remainder that “a rat is not a monkey is not a human”, in the famous words of A. D. (Bud) Craig (2009).

Mohan et al. (2015) analyzed a portion of the brain (Brodmann area 21) obtained from 28 individuals that had to undergo neurosurgery and have it removed for various illnesses. Using some good microscopy, fancy statistics, and 3-D modeling, they reconstructed the shape of individual neurons from that region. The main finding is that 88% of human pyramidal neurons were distinctly different than their mouse or macaque counterparts. Also, they managed to record the electrical activity of these neurons in less than 10 minutes after resection. So it appears that this morphological distinctness of ours results in unique electrical properties of human neurons, which may account for the “distinct cognitive capabilities of humans”, as the authors put it.

Approximate location of Brodmann Area 21, corresponding to gyrus temporalis medium. Credit: Brain template to _DJ_; Area tracing to Neuronicus
Approximate location of Brodmann Area 21, corresponding to gyrus temporalis medium. Credit: Brain template to _DJ_; Area tracing to Neuronicus

Citation: Mohan, H., Verhoog, M. B., Doreswamy, K. K., Eyal, G., Aardse, R., Lodder, B. N., Goriounova, N. A., Asamoah, B., B. Brakspear, A. B. C., Groot, C., van der Sluis, S., Testa-Silva, G., Obermayer, J., Boudewijns, Z. S., Narayanan, R. T., Baayen, J. C., Segev, I., Mansvelder, H. D., de Kock, C. P. (28 August 2015; Epub ahead of print). Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex. Cerebral Cortex, 1-15. doi: 10.1093/cercor/bhv188. Article + FREE PDF