New Promising Therapeutic Avenues of Curcumin in Brain Diseases

Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called "spice of life", in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer's Diseases, Parkinson's Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders

Degradation of EEG microstates patterns in subjective cognitive decline and mild cognitive impairment: Early biomarkers along the Alzheimer's Disease continuum?

Alzheimer's disease (AD) pathological changes may begin up to decades earlier than the appearance of the first symptoms of cognitive decline. Subjective cognitive decline (SCD) could be the first pre-clinical sign of possible AD, which might be followed by mild cognitive impairment (MCI), the initial stage of clinical cognitive decline. However, the neural correlates of these prodromic stages are not completely clear yet. Recent studies suggest that EEG analysis tools characterizing the cortical activity as a whole, such as microstates and cortical regions connectivity, might support a characterization of SCD and MCI conditions. Here we test this approach by performing a broad set of analyses to identify the prominent EEG markers differentiating SCD (n = 57), MCI (n = 46) and healthy control subjects (HC, n = 19). We found that the salient differences were in the temporal structure of the microstates patterns, with MCI being associated with less complex sequences due to the altered transition probability, frequency and duration of canonic microstate C. Spectral content of EEG, network connectivity, and spatial arrangement of microstates were instead largely similar in the three groups. Interestingly, comparing properties of EEG microstates in different cerebrospinal fluid (CSF) biomarkers profiles, we found that canonic microstate C displayed significant differences in topography in AD-like profile. These results show that the progression of dementia might be associated with a degradation of the cortical organization captured by microstates analysis, and that this leads to altered transitions between cortical states. Overall, our approach paves the way for the use of non-invasive EEG recordings in the identification of possible biomarkers of progression to AD from its prodromal states

Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia

BackgroundPlasma biomarkers are preferable to invasive and expensive diagnostic tools, such as neuroimaging and lumbar puncture that are gold standard in the clinical management of Alzheimer’s Disease (AD). Here, we investigated plasma Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NfL) and Phosphorylated-tau-181 (pTau 181) in AD and in its early stages: Subjective cognitive decline (SCD) and Mild cognitive impairment (MCI).Material and methodsThis study included 152 patients (42 SCD, 74 MCI and 36 AD). All patients underwent comprehensive clinical and neurological assessment. Blood samples were collected for Apolipoprotein E (APOE) genotyping and plasma biomarker (GFAP, NfL, and pTau 181) measurements. Forty-three patients (7 SCD, 27 MCI, and 9 AD) underwent a follow-up (FU) visit after 2 years, and a second plasma sample was collected. Plasma biomarker levels were detected using the Simoa SR-X technology (Quanterix Corp.). Statistical analysis was performed using SPSS software version 28 (IBM SPSS Statistics). Statistical significance was set at p < 0.05.ResultsGFAP, NfL and pTau 181 levels in plasma were lower in SCD and MCI than in AD patients. In particular, plasma GFAP levels were statistically significant different between SCD and AD (p=0.003), and between MCI and AD (p=0.032). Plasma NfL was different in SCD vs MCI (p=0.026), SCD vs AD (p<0.001), SCD vs AD FU (p<0.001), SCD FU vs AD (p=0.033), SCD FU vs AD FU (p=0.011), MCI vs AD (p=0.002), MCI FU vs AD (p=0.003), MCI FU vs AD FU (p=0.003) and MCI vs AD FU (p=0.003). Plasma pTau 181 concentration was significantly different between SCD and AD (p=0.001), MCI and AD (p=0.026), MCI FU and AD (p=0.020). In APOE ϵ4 carriers, a statistically significant increase in plasma NfL (p<0.001) and pTau 181 levels was found (p=0.014). Moreover, an association emerged between age at disease onset and plasma GFAP (p = 0.021) and pTau181 (p < 0.001) levels.Discussion and conclusionsPlasma GFAP, NfL and pTau 181 are promising biomarkers in the diagnosis of the prodromic stages and prognosis of dementia

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

BACKGROUND: Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer’s Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD. METHODS: We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping. RESULTS: The proportion between women and men was significantly different (68.7% [95% CI 63.9–73.4 vs 31.4%, 95% CI 26.6–36.0]). Women were younger than men at onset of SCD and at the baseline visit (p = 0.021), had lower years of education (p = 0.007), lower TIB scores (p < 0.001), and higher MAC-Q scores (p = 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men. CONCLUSIONS: Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women

CAG Repeats Within the Non-pathological Range in the HTT Gene Influence Personality Traits in Patients With Subjective Cognitive Decline: A 13-Year Follow-Up Study

OBJECTIVE: HTT is a gene containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. HTT genes with <35 repeats are not associated with HD. The biological function of CAG repeat expansion below the non-pathological threshold is not well understood. In fact higher number of repeats in HTT confer advantageous changes in brain structure and general intelligence, but several studies focused on establishing the association between CAG expansions and susceptibility to psychiatric disturbances and to other neurodegenerative disease than HD. We hypothesized that HTT CAG repeat length below the pathological threshold might influence mood and personality traits in a longitudinal sample of individuals with Subjective Cognitive Decline. METHODS: We included 54 patients with SCD. All patients underwent an extensive neuropsychological battery at baseline, APOE genotyping and analysis of HTT alleles. We used the Big Five Factors Questionnaire (BFFQ) and Hamilton Depression Rating Scale (HDRS), respectively, to assess personality traits of patients and depression at baseline. Patients who did not progress to Mild Cognitive Impairment (MCI) had at least 5-year follow-up time. RESULTS: In the whole sample, CAG repeat number in the shorter HTT allele was inversely correlated with conscientiousness (Pearson = −0.364, p = 0.007). There was no correlation between HDRS and CAG repeats. During the follow-up, 14 patients [25.93% (95% C.I. = 14.24–37.61)] progressed to MCI (MCI(+)) and 40 [74.07% (95% C.I. = 62.39–85.76)] did not (MCI(−)). When we performed the same analysis in the MCI(+) group we found that: CAG repeat length on the shorter allele was inversely correlated with energy (Pearson = 0.639, p = 0.014) and conscientiousness (Pearson = −0.695, p = 0.006). CAG repeat length on the longer allele was inversely correlated with conscientiousness (Pearson = −0.901, p < 0.001) and directly correlated with emotional stability (Pearson = 0.639, p = 0.014). These associations were confirmed also by multivariate analysis. We found no correlations between BFFQ parameters and CAG repeats in the MCI(−) group. DISCUSSION: Personality traits and CAG repeat length in the intermediate range have been associated with progression of cognitive decline and neuropathological findings consistent with AD. We showed that CAG repeat lengths in the HTT gene within the non-pathological range influence personality traits

The Effects of Curcumin on Inflammasome: Latest Update

Curcumin, a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of different diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. Curcumin is generally beneficial to improve human health with anti-inflammatory and antioxidative properties as well as antitumor and immunoregulatory properties. Inflammasomes are NLR family, pyrin domain-containing 3 (NLRP3) proteins that are activated in response to a variety of stress signals and that promote the proteolytic conversion of pro-interleukin-1β and pro-interleukin-18 into active forms, which are central mediators of the inflammatory response; inflammasomes can also induce pyroptosis, a type of cell death. The NLRP3 protein is involved in a variety of inflammatory pathologies, including neurological and autoimmune disorders, lung diseases, atherosclerosis, myocardial infarction, and many others. Different functional foods may have preventive and therapeutic effects in a wide range of pathologies in which inflammasome proteins are activated. In this review, we have focused on curcumin and evidenced its therapeutic potential in inflammatory diseases such as neurodegenerative diseases, respiratory diseases, and arthritis by acting on the inflammasome