Alzheimer’s Disease: What Can We Learn From the Peripheral Olfactory System?

Dibattista, Michele; Pifferi, Simone; Menini, Anna; Reisert, Johannes

doi:10.3389/fnins.2020.00440

Cited by 36 publications

(36 citation statements)

References 180 publications

(239 reference statements)

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“…As early symptoms of AD include functional deficit of smell and vision, olfactory and vision biomarkers are suggested to serve as noninvasive biomarkers to diagnose dementia (Romano et al, 2021). In AD patients or AD mice, beta-amyloid deposition is found in the olfactory bulb [reviewed by Dibattista et al (2020)]. In the 5xFAD mice, besides hippocampal region, we also found an accumulation of Aβ in the olfactory bulb and visual cortex, confirming the AD pathology in various brain regions in 5xFAD mice.…”

Section: Discussionsupporting

confidence: 70%

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

et al. 2021

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One of the major challenges in treating Alzheimer's disease (AD) is its early diagnosis. Increasing data from clinical and animal research indicate that the retina may facilitate an early diagnosis of AD. However, a previous study on the 5xFAD (a fast AD model), showing retinal changes before those in the brain, has been questioned because of the involvement of the retinal degeneration allele Pde6brd1. Here, we tested in parallel, at 4 and 6 months of age, both the retinal and the brain structure and function in a 5xFAD mouse line that carries no mutation of rd1. In the three tested regions of the 5xFAD brain (hippocampus, visual cortex, and olfactory bulb), the Aβ plaques were more numerous than in wild-type (WT) littermates already at 4 months, but deterioration in the cognitive behavioral test and long-term potentiation (LTP) lagged behind, showing significant deterioration only at 6 months. Similarly in the retina, structural changes preceded functional decay. At 4 months, the retina was generally normal except for a thicker outer nuclear layer in the middle region than WT. At 6 months, the visual behavior (as seen by an optomotor test) was clearly impaired. While the full-field and pattern electroretinogram (ERG) responses were relatively normal, the light responses of the retinal ganglion cells (measured with multielectrode-array recording) were decreased. Structurally, the retina became abnormally thick with few more Aβ plaques and activated glia cells. In conclusion, the timeline of the degenerative processes in the retina and the brain is similar, supporting the use of non-invasive methods to test the retinal structure and function to reflect changes in the brain for early AD diagnosis.

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Section: Discussionsupporting

confidence: 70%

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

et al. 2021

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“…Although sustentacular cells are not directly involved in the conversion of a chemical odor signal into an electrical nerve signal by olfactory receptor neurons that is then sent to the brain, they regulate several aspects of the tissue homeostasis, which in turn assures a normal function of olfactory receptor neurons ( Dibattista et al 2020 ). All these events could drive a partial or complete loss of smell.…”

Section: Discussionmentioning

confidence: 99%

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19

et al. 2020

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The purpose of our cohort study was to quantify olfactory deficits in COVID-19 patients using Sniffin’ Sticks and a pre-post design to evaluate olfactory recovery. 30 adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin’ Sticks Test (SST, Burghardt®, Wedel, Germany) considering olfactory threshold (T), odor discrimination (D) and odor identification (I). Results were presented as a composite TDI score (range 1–48) used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 <TDI< 30.5) or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (VAS rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale-HRS). Patients were tested during hospitalization and about two months after symptoms onset. During the hospitalization the overall TDI score indicated that our cohort had impairments in their olfactory ability (10 % was diagnosed with Anosmia and more than 50 % were hyposmic). Almost all patients showed a significant improvement at around one month following the first test and for all the parts of the SST except for odor identification. None of the subjects at one month was still diagnosed with Anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and two months after symptoms’ onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.

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“…Olfactory deficits have been previously reported for several viral infections, 12,134 and are characteristic of neurodegenerative disorders. [135][136][137][138][139] Notably, anosmia is linked to high levels of interleukin-6, an inflammatory mediator causally involved in brain disorders whose actions are blocked by tocilizumab as part of COVID-19 treatment. 140 Systematic reviews 141,142 and meta-analysis data 143,144 have firmly established incident and prevalent stroke as independent risk factors of dementia.…”

Section: Implications For Neuropsychiatric Disordersmentioning

confidence: 99%

The chronic neuropsychiatric sequelae of COVID‐19: The need for a prospective study of viral impact on brain functioning

Erausquin

Snyder

Carrillo

et al. 2021

Alzheimer's & Dementia

164

154

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Introduction:The increasing evidence of SARS-CoV-2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia.Methods: The Alzheimer's Association and representatives from more than 30 countries-with technical guidance from the World Health Organization-have formed an international consortium to study the short-and long-term consequences of SARS-CoV-2 on the CNS-including the underlying biology that may contribute to AD and other dementias. This consortium will link teams from around the world covering more than 22 million COVID-19 cases to enroll two groups of individuals including people with disease, to be evaluated for follow-up evaluations at 6, 9, and 18 months, and people who are already enrolled in existing international research studies to add additional measures and markers of their underlying biology. Conclusions:The increasing evidence and understanding of SARS-CoV-2's impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. This program of studies aims to better understand the long-term consequences that may impact the brain, cognition, and functioning-including the underlying biology that may contribute to AD and other dementias.

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Alzheimer’s Disease: What Can We Learn From the Peripheral Olfactory System?

Cited by 36 publications

References 180 publications

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19

The chronic neuropsychiatric sequelae of COVID‐19: The need for a prospective study of viral impact on brain functioning

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