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



I can watch you learning

Human Stereotaxic System. Photo credit: The Mind Project
Human Stereotaxic System. Photo credit: The Mind Project

Recording directly form the healthy living human brain has always been a coveted goal of many neuroscientists, thus bypassing the limitations of non-invasive techniques or animal work. But, understandably, nobody would seek or grant approval for inserting an electrode in the healthy living human brain, on moral and ethical grounds. The next best thing is to insert an electrode into the not so healthy living human brain.

Ison, Quiroga, & Fried (2015) got lucky and gained access to 14 patients with intractable epilepsy that had electrodes implanted in their brain to find where the seizure focus is (for possible surgical resection later on). Using these electrodes, they recorded the activity of single neurons within the medial temporal lobe (MTL, a brain area paramount for learning) while the patients performed some simple association tasks. First, they presented images of places, people, and animals to the patients to see “which (if any) of the recorded neurons responded to a picture” (p. 220). When they got a neuron responding to something, they rushed out, did some data and image processing, and after an hour they started the experiment. Which was showing the patient the picture to which the neuron responded to (e.g. Stimulus 1 = patient’s daughter) overimposed on a background that the neuron did not respond to (e.g. Stimulus 2 = the Eiffel tower). After one single trial (although there was some variability), the patients learned the associations (i.e. Stimulus 3 = daughter in front of Eiffel tower) and this learning was mirrored by how the neuron responded. Namely, the neuron increased its activity by 200% to 400% (counted in spikes per second) when shown the previously un-responded to image alone (i.e. Stimulus 2).

Excerpt from Fig. 5 from Ison, Quiroga, & Fried (2015).
Excerpt from Fig. 5 from Ison, Quiroga, & Fried (2015). “Average normalized neural activity (black squares) and behavioral responses (green circles) to the non-preferred stimulus as a function of trial number. Data were aligned to the learning time (relative trial number 0)”, i.e. when they showed the composite image between Stimulus 1 and Stimulus 2. “Note that the neural activity follows the sudden increase in behavioral learning”.

The authors recorded from over 600 neurons from various MTL regions, out of which 51 responded to a Stimulus 1. From these, only half learned, that is, they increased their activity when Stimulus 2 was shown. For the picky specialist, the cells were both Type 1 and Type 2 neurons, located 6 in the hippocampus, 4 in the entorhinal cortex, 11 in the parahippocampal cortex, and 1 in the amygdala. And the authors controlled for familiarity, attentional demands, and other extraneous variables (with some very fancy and hard to follow stats, I might add).

The paper settles an old psychology dispute. Do we learn an association gradually or at once? In other words, do we learn gradually that A and B occur together, or do we learn that the first time we are shown A and B together and the next trials serve just to refine and consolidate the new knowledge? Ison, Quiroga, & Fried (2015) data show that learning happens at once, in an all-or-none fashion.

Reference: Ison, M. J., Quian Quiroga, R., & Fried, I. (1 July 2015). Rapid Encoding of New Memories by Individual Neurons in the Human Brain. Neuron, 87(1): 220-30. doi: 10.1016/j.neuron.2015.06.016. Article | FREE PDF

By Neuronicus, 4 October 2015