Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19.

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19 + patients.

Lengacher NA ，Tomlinson JJ ，Jochum AK ，Franz J ，Hasan Ali O ，Flatz L ，Jochum W ，Penninger J ，aSCENT-PD Investigators ，Stadelmann C ，Woulfe JM ，Schlossmacher MG ... -  《Acta Neuropathologica Communications》

Tau pathology in the olfactory bulb correlates with Braak stage, Lewy body pathology and apolipoprotein epsilon4.

Tsuboi Y ，Wszolek ZK ，Graff-Radford NR ，Cookson N ，Dickson DW ... -  《NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY》

Increased amoeboid microglial density in the olfactory bulb of Parkinson's and Alzheimer's patients.

The olfactory bulb (OB) is affected early in both Parkinson's (PD) and Alzheimer's disease (AD), evidenced by the presence of disease-specific protein aggregates and an early loss of olfaction. Whereas previous studies showed amoeboid microglia in the classically affected brain regions of PD and AD patients, little was known about such changes in the OB. Using a morphometric approach, a significant increase in amoeboid microglia density within the anterior olfactory nucleus (AON) of AD and PD patients was observed. These amoeboid microglia cells were in close apposition to β-amyloid, hyperphosphorylated tau or α-synuclein deposits, but no uptake of pathological proteins by microglia could be visualized. Subsequent analysis showed (i) no correlation between microglia and α-synuclein (PD), (ii) a positive correlation with β-amyloid (AD), and (iii) a negative correlation with hyperphosphorylated tau (AD). Furthermore, despite the observed pathological alterations in neurite morphology, neuronal loss was not apparent in the AON of both patient groups. Thus, we hypothesize that, in contrast to the classically affected brain regions of AD and PD patients, within the AON rather than neuronal loss, the increased density in amoeboid microglial cells, possibly in combination with neurite pathology, may contribute to functional deficits.

Doorn KJ ，Goudriaan A ，Blits-Huizinga C ，Bol JG ，Rozemuller AJ ，Hoogland PV ，Lucassen PJ ，Drukarch B ，van de Berg WD ，van Dam AM ... -  《-》

Microglia is associated with p-Tau aggregates in the olfactory bulb of patients with neurodegenerative diseases.

Carmona-Abellan M ，Martinez-Valbuena I ，Marcilla I ，DiCaudo C ，Gil I ，Nuñez J ，Luquin MR ... -  《-》

Co-localization of tau and alpha-synuclein in the olfactory bulb in Alzheimer's disease with amygdala Lewy bodies.

Fujishiro H ，Tsuboi Y ，Lin WL ，Uchikado H ，Dickson DW ... -  《-》