Comparison of Olfactory Tract Diffusion Measures Between Early Stage Parkinson’s Disease Patients and Healthy Controls Using Ultra-High Field MRI

Heijmans, Margot; Wolters, Amée F.; Temel, Yasin; Kuijf, Mark L.; Michielse, Stijn

doi:10.3233/jpd-223349

Cited by 3 publications

(2 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, atrophy, and changes in the structural integrity of OT has been also observed in PD subjects with respect to controls [ 13 ]. Besides, OT MRI diffusion measures are not adequate as early clinical biomarker for PD [ 14 ]. OT volume is smaller in PD than other movement disorders, such as Multiple system atrophy (MSA), Progressive supranuclear palsy (PSP), and Corticobasal degeneration (CBD) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory–entorhinal–amygdaloid axis in Alzheimer’s and Parkinson’s diseases

et al. 2023

View full text Add to dashboard Cite

Background Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-pathological mechanisms and potential therapeutic targets associated with olfactory dysfunction. Methods SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) and bioinformatic workflows were applied in 57 post-mortem olfactory tracts (OT) derived from controls with no known neurological history (n = 6F/11M), AD (n = 4F/13M) and PD (n = 7F/16M) subjects. Complementary molecular analyses by Western-blotting were performed in the olfactory bulb (OB), entorhinal cortex (EC) and amygdala areas. Results 327 and 151 OT differentially expressed proteins (DEPs) were observed in AD women and AD men, respectively (35 DEPs in common). With respect to PD, 198 DEPs were identified in PD women, whereas 95 DEPs were detected in PD men (20 DEPs in common). This proteome dyshomeostasis induced a disruption in OT protein interaction networks and widespread sex-dependent pathway perturbations in a disease-specific manner, among them Sirtuin (SIRT) signaling. SIRT1, SIRT2, SIRT3 and SIRT5 protein levels unveiled a tangled expression profile across the olfactory–entorhinal–amygdaloid axis, evidencing disease-, sex- and brain structure-dependent changes in olfactory protein acetylation. Conclusions Alteration in the OT proteostasis was more severe in AD than in PD. Moreover, protein expression changes were more abundant in women than men independent of the neurological syndrome. Mechanistically, the tangled SIRT profile observed across the olfactory pathway-associated brain regions in AD and PD indicates differential NAD (+)-dependent deacetylase mechanisms between women and men. All these data shed new light on differential olfactory mechanisms across AD and PD, pointing out that the evaluation of the feasibility of emerging sirtuin-based therapies against neurodegenerative diseases should be considered with caution, including further sex dimension analyses in vivo and in clinical studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory–entorhinal–amygdaloid axis in Alzheimer’s and Parkinson’s diseases

et al. 2023

View full text Add to dashboard Cite

show abstract

“…On the other hand, atrophy, and changes in the structural integrity of OT has been also observed in PD subjects with respect to controls [13]. Besides, OT MRI diffusion measures are not adequate as early clinical biomarker for PD [14]. OT volume is smaller in PD than PD-related disorders such as Multiple system atrophy (MSA), Progressive supranuclear palsy (PSP), and Corticobasal degeneration (CBD) [15].…”

Section: Introductionmentioning

confidence: 99%

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer´s and Parkinson´s diseases

Cartas-Cejudo

Lachén-Montes

Ferrer

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Smell impairment is one of the earliest features in Alzheimer’s (AD) and Parkinson’s diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-pathological mechanisms and potential therapeutic targets associated to olfactory dysfunction. Methods: SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) and bioinformatic workflows were applied in 57 postmortem olfactory tracts (OT) derived from non-demented (n=6F/11M), AD (n=4F/13M) and PD (n=7F/16M) subjects. Complementary molecular analyses by Western-blotting were performed in the olfactory bulb (OB), entorhinal cortex (EC) and amygdala areas. Results: 327 and 151 OT differentially expressed proteins (DEPs) were observed in AD women and AD men respectively (35 DEPs in common). Respect to PD, 198 DEPs were identified in PD women whereas 95 DEPs were detected in PD men (20 DEPs in common). This proteome dyshomeostasis induced a disruption in OT protein interaction networks and widespread sex-dependent pathway perturbations in a disease-specific manner, among them Sirtuin (SIRT) signaling. SIRT1, SIRT2, SIRT3 and SIRT5 protein levels unveiled a tangled expression profile across the olfactory-entorhinal-amygdaloid axis, evidencing disease- sex- and brain structure-dependent changes in olfactory protein acetylation. Conclusions: Alteration in the OT proteostasis was more severe in AD than in PD. Moreover, protein expression changes were more abundant in women than men independent of the neurological syndrome. Mechanistically, the tangled SIRT profile observed across the olfactory pathway-associated brain regions in AD and PD indicates differential NAD (+)-dependent deacetylase mechanisms between women and men. All these data shed new light on differential olfactory mechanisms across AD and PD, pointing out that the evaluation of the feasibility of emerging sirtuin-based therapies against neurodegenerative diseases should be considered with caution, including further sex dimension analyses in vivo and in clinical studies.

show abstract

Structural and Functional Connectomics of the Olfactory System in Parkinson’s Disease: a Systematic Review

Ielo,

Bonanno,

Brunati

et al. 2024

Parkinsonism & Related Disorders

View full text Add to dashboard Cite

Comparison of Olfactory Tract Diffusion Measures Between Early Stage Parkinson’s Disease Patients and Healthy Controls Using Ultra-High Field MRI

Cited by 3 publications

References 42 publications

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory–entorhinal–amygdaloid axis in Alzheimer’s and Parkinson’s diseases

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory–entorhinal–amygdaloid axis in Alzheimer’s and Parkinson’s diseases

Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer´s and Parkinson´s diseases

Structural and Functional Connectomics of the Olfactory System in Parkinson’s Disease: a Systematic Review

Contact Info

Product

Resources

About