Region-specific changes in gene expression are associated with cognitive deficits in the alpha-synuclein-induced model of Parkinson's disease: A transcriptomic profiling study

Manchinu, Maria Francesca; Pala, Mauro; Palmas, Maria Francesca; Diana, Maria Antonietta; Maschio, Andrea; Etzi, Michela; Pisanu, Augusta; Diana, Francesca Isabella; Marongiu, Jacopo; Mansueto, Silvia; Carboni, Ezio; Fusco, Giuliana; De Simone, Alfonso; Carta, Anna R.

doi:10.1016/j.expneurol.2023.114651

Cited by 3 publications

(1 citation statement)

References 76 publications

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“…These findings suggest a transport of CNS aSyn to the periphery which could help clinicians to detect by non-invasive practices aSyn levels as early as possible serving as a potential surrogate biomarker of risk of cognitive impairment. A recent transcriptomic study in an aSyn-based brain model of PD shows region-specific gene expression changes associated with cognitive deficit [149].…”

Section: Cognitive Impairmentmentioning

confidence: 99%

Alpha Synuclein Toxicity and Non-motor Parkinson’s

Mazzotta,

Conte

2024

Preprint

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Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

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Section: Cognitive Impairmentmentioning

confidence: 99%

Alpha Synuclein Toxicity and Non-motor Parkinson’s

Mazzotta,

Conte

2024

Preprint

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Mild cognitive impairment in Parkinson's disease: current view

Jellinger

2024

Front. Cognit.

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Parkinson's disease (PD), the most common motor movement disorder and second most common neurodegenerative disorder after Alzheimer's disease (AD), is often preceded by a period of mild cognitive impairment (MCI), which is associated with impairment of a variety of cognitive domains including executive function, attention, visuospatial abilities and memory. MCI, a risk factor for developing dementia, affects around 30% of de novo PD patients and can increase to 75% after more than 10 years. While 30–40% remain in the MCI state, up to 60% will convert to dementia. Characteristic findings are slowing of EEG rhythms, frontotemporal hypoperfusion, decreased functional connectivity in the default mode and attentional networks, prefrontal and basal-ganglia-cortical circuits, which often manifests prior to clinical symptoms and overt brain atrophy. The heterogeneity of cognitive phenotypes suggests that a common neurodegenerative process affects multiple functional neuronal networks and neuromodulatory systems that may be superimposed by Lewy body and Alzheimer's-related or other co-pathologies. Sparse neuropathological data for PD-MCI revealed a heterogenous picture with various morphological changes similar to MCI in other diseases. This review highlights the essential epidemiological, clinical, neuroimaging and morphological changes in PD-MCI, available biomarkers, and discusses the heterogenous pathobiological mechanisms involved in its development. In view of its complex pathogenesis, well-designed longitudinal clinico-pathological studies are warranted to clarify the alterations leading to MCI in PD, which may be supported by fluid and neuroimaging biomarkers as a basis for early diagnosis and future adequate treatment modalities of this debilitating disorder.

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Alpha Synuclein Toxicity and Non-Motor Parkinson’s

Mazzotta,

Conte

2024

Cells

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Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population over the age of 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (αSyn)-rich Lewy bodies both manifesting with classical motor signs. αSyn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considered prevalent among individuals prior to PD diagnosis and persisting throughout the patient’s life. NMS mainly includes loss of taste and smell, constipation, psychiatric disorders, dementia, impaired rapid eye movement (REM) sleep, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings on the impact of αSyn deposits on several prodromal NMS and emphasizes the importance of early detection of αSyn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

show abstract

Region-specific changes in gene expression are associated with cognitive deficits in the alpha-synuclein-induced model of Parkinson's disease: A transcriptomic profiling study

Cited by 3 publications

References 76 publications

Alpha Synuclein Toxicity and Non-motor Parkinson’s

Alpha Synuclein Toxicity and Non-motor Parkinson’s

Mild cognitive impairment in Parkinson's disease: current view

Alpha Synuclein Toxicity and Non-Motor Parkinson’s

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