Oliver, J. C. | bioRxiv Science

bioRxiv2019

Severe Hyposmia Distinguishes Neuropathologically Confirmed Dementia with Lewy Bodies from Alzheimer’s Disease Dementia

Due to the absence of core clinical features, many subjects with neuropathologically-confirmed dementia with Lewy bodies (DLB) are never diagnosed as such during life. Most of these are diagnosed with Alzheimers disease dementia (ADD) or unspecified dementia. Unrecognized DLB therefore is a critical impediment to clinical studies and treatment trials of both ADD and DLB. There are numerous published studies that suggest that olfactory function tests may be able to differentiate some neurodegenerative conditions from each other and from normal subjects, but there are very few studies with neuropathological confirmation of diagnosis. We compared University of Pennsylvania Smell Identification Test (UPSIT) results in 209 subjects: 1) 29 concurrently meeting intermediate or high consensus clinicopathological criteria for both DLB and ADD 2) 96 meeting criteria for ADD without DLB 3) 84 control subjects that were non-demented and without parkinsonism at death. The DLB subjects had significantly lower (one-way ANOVA p < 0.0001, pairwise Bonferroni p < 0.05) first and mean UPSIT scores (13.7 and 13.2) than ADD (23.3 and 22.2) or controls (29.6 and 28.9). For subjects with first and mean UPSIT scores less than 20 and 17, respectively, Firth logistic regression analysis, adjusted for age, gender and mean MMSE score, conferred statistically significant odds ratios of 17.5 and 18.0 for predicting a DLB vs ADD diagnosis, as compared to 3.3 for the presence or absence of visual hallucinations throughout the clinical observation period. To our knowledge, this is the largest study to date comparing olfactory function in subjects with neuropathologically confirmed DLB and ADD. Olfactory function testing may be a convenient and inexpensive strategy for enriching dementia studies or clinical trials with DLB subjects, or conversely, reducing the inclusion of DLB subjects in ADD studies or trials.

neuroscience↗

bioRxiv2018

Step-wise evolution of temperature-mediated phenotypic plasticity in eyespot size across nymphalid butterflies

There are two disparate views regarding phenotypic plasticity. One regards plasticity as a derived adaptation to help organisms survive in variable environments1, 2 while the other views plasticity as the outcome of flexible, non-canalized, developmental processes, ancestrally present in most organisms, that helps them colonize or adapt to novel environments3-5 e.g., a pre-adaptation. Both views of plasticity currently lack a rigorous, mechanistic examination of ancestral and derived states and direction of change2. Here we show that the origin of phenotypic plasticity in eyespot size in response to environmental temperature observed in Bicyclus anynana butterflies is a derived adaptation of this lineage. Eyespot size is regulated by temperature-mediated changes in levels of a steroid hormone, 20E, that affects proliferation of eyespot central cells expressing the 20E receptor (EcR)6, 7. By estimating the origin of the known physiological and molecular components of eyespot size plasticity in a comparative framework, we showed that 20E titer plasticity in response to temperature is a pre-adaptation shared by all butterfly species examined, whereas the origin of expression of EcR in eyespot centers, and the origin of eyespot sensitivity to the hormone-receptor complex are both derived traits found only in a subset of species with eyespots. The presence of all three molecular components required to produce a plastic response is only observed in B. anynana. This gradual, step-wise, physiological/molecular response to temperature is a likely adaptation to temperature variation experienced across wet and dry seasons in the habitat of this species. This work supports, thus, the first view of plasticity as a derived adaptation.

evolutionary biology↗