A Critical Proton MR Spectroscopy Marker of Alzheimer’s Disease Early Neurodegenerative Change: Low Hippocampal NAA/Cr Ratio Impacts APOE ε4 Mexico City Children and Their Parents

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Antonieta Mora-Tiscareño ◽  
Gastón Melo-Sánchez ◽  
Joel Rodríguez-Díaz ◽  
Ricardo Torres-Jardón ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Mexico City ◽  
Density Functional ◽  
Fine Particulate Matter ◽  
Healthy Children ◽  
1H Mrs ◽  
Apoe Ε4 ◽  
The Right

Severe air pollution exposures produce systemic, respiratory, myocardial, and brain inflammation and Alzheimer’s disease (AD) hallmarks in clinically healthy children. We tested whether hippocampal metabolite ratios are associated with contrasting levels of air pollution, APOE, and body mass index (BMI) in paired healthy children and one parent sharing the same APOE alleles. We used 1H-MRS to interrogate bilateral hippocampal single-voxel in 57 children (12.45 ± 3.4 years) and their 48 parents (37.5 ± 6.78 years) from a low pollution city versus Mexico City (MC). NAA/Cr, Cho/Cr, and mI/Cr metabolite ratios were analyzed. The right hippocampus NAA/Cr ratio was significantly different between cohorts (p = 0.007). The NAA/Cr ratio in right hippocampus in controls versus APOE ε4 MC children and in left hippocampus in MC APOE ε4 parents versus their children was significantly different after adjusting for age, gender, and BMI (p = 0.027 and 0.01, respectively). The NAA/Cr ratio is considered reflective of neuronal density/functional integrity/loss of synapses/higher pTau burden, thus a significant decrease in hippocampal NAA/Cr ratios may constitute a spectral marker of early neurodegeneration in young urbanites. Decreases in NAA/Cr correlate well with cognitive function, behavioral symptoms, and dementia severity; thus, since the progression of AD starts decades before clinical diagnosis, our findings support the hypothesis that under chronic exposures to fine particulate matter and ozone above the standards, neurodegenerative processes start in childhood and APOE ε4 carriers are at higher risk. Gene and environmental factors are critical in the development of AD and the identification and neuroprotection of young urbanites at high risk must become a public health priority.

Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer’s Disease Development in Mexico City Young Females

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Suzanne M. de la Monte
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
High Risk ◽  
Mexico City ◽  
Cognitive Deficits ◽  
Central Nervous System Involvement ◽  
High Risk Group ◽  
Polycyclic Aromatic

Given the epidemiological trends of increasing Alzheimer’s disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Mexico City children experienced pre- and postnatal high exposures to PM2.5, O3, combustion-derived iron-rich nanoparticles, metals, polycyclic aromatic hydrocarbons, and endotoxins. Exposures are associated with early brain gene imbalance in oxidative stress, inflammation, innate and adaptive immune responses, along with epigenetic changes, accumulation of misfolded proteins, cognitive deficits, and brain structural and metabolic changes. The Apolipoprotein E (APOE) 4 allele, the most prevalent genetic risk for AD, plays a key role in the response to air pollution in young girls. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5–2 SD from average IQ). This review focused on the relationships between gender, BMI, systemic and neural inflammation, insulin resistance, hyperleptinemia, dyslipidemia, vascular risk factors, and central nervous system involvement in APOE4 urbanites exposed to PM2.5 and magnetite combustion-derived iron-rich nanoparticles that can reach the brain. APOE4 young female heterozygous carriers constitute a high-risk group for a fatal disease: AD. Multidisciplinary intervention strategies could be critical for prevention or amelioration of cognitive deficits and long-term AD progression in young individuals at high risk.

Air Pollution, Combustion and Friction Derived Nanoparticles, and Alzheimer’s Disease in Urban Children and Young Adults

2021 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Angélica González-Maciel ◽  
Randy J. Kulesza ◽  
Luis Oscar González-González ◽  
Rafael Reynoso-Robles ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Young Adults ◽  
Particulate Matter ◽  
Mexico City ◽  
Neurofibrillary Tangle ◽  
Rapid Progression ◽  
Us Epa ◽  
Children And Young Adults

Exposures to fine particulate matter (PM2.5) and ozone (O3)≥US EPA standards are associated with Alzheimer’s disease (AD) risk. The projection of 13.8 million AD cases in the US by the year 2050 obligate us to explore early environmental exposures as contributors to AD risk and pathogenesis. Metropolitan Mexico City children and young adults have lifetime exposures to PM2.5 and O3, and AD starting in the brainstem and olfactory bulb is relentlessly progressing in the first two decades of life. Magnetite combustion and friction-derived nanoparticles reach the brain and are associated with early and progressive damage to the neurovascular unit and to brain cells. In this review: 1) we highlight the interplay environment/genetics in the AD development in young populations; 2) comment upon ApoE ε4 and the rapid progression of neurofibrillary tangle stages and higher suicide risk in youth; and 3) discuss the role of combustion-derived nanoparticles and brain damage. A key aspect of this review is to show the reader that air pollution is complex and that profiles change from city to city with common denominators across countries. We explore and compare particulate matter profiles in Mexico City, Paris, and Santiago in Chile and make the point of why we should invest in decreasing PM2.5 to at least our current US EPA standard. Multidisciplinary intervention strategies are critical for prevention or amelioration of cognitive deficits and AD progression and risk of suicide in young individuals. AD pathology evolving from childhood is threating the wellbeing of future generations.

Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease

2016 ◽  
Vol 146 ◽  
pp. 404-417 ◽  
Author(s):  
Lilian Calderón-Garcidueñas ◽  
Rafael Reynoso-Robles ◽  
Javier Vargas- Martínez ◽  
Aline Gómez-Maqueo-Chew ◽  
Beatriz Pérez-Guillé ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
White Matter ◽  
Mexico City ◽  
Neurovascular Unit ◽  
Potential Impact ◽  
White Matter Pathology

scholarly journals Knowledge and Awareness on Air Pollution as A Risk Factor for Alzheimer’s Disease and Dementia- A Survey

2020 ◽  
Vol 11 (SPL3) ◽  
pp. 694-699
Author(s):  
Hemaahini Tamilmani ◽  
Gayathri Devi R ◽  
Gayathri R
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Air Pollution ◽  
Elderly People ◽  
Fine Particulate Matter ◽  
Global Risk ◽  
Future Studies ◽  
Fine Particulate ◽  
Spss Software ◽  
Behaviour Changes

Dementia is a syndrome where the memory deteriorates, thinking changes, behaviour changes, etc. It can get developed from Alzheimer's disease and mainly affects elderly people. The fine particulate matter present in the air can increase the risk of cardiovascular problems which can lead to dementia. The main aim of this research is to understand the knowledge and awareness of people on the topic of air pollution linked to dementia. A survey was designed to analyse the result. The questionnaire was prepared in Google Forms- website and was distributed to 100 participants. The questionnaire was based on dementia and air pollution and its relation. The data was then collected and statistically analysed using SPSS software. 71% of the participants were aware that both air pollution and dementia are increasing factors of global risk. And only 77% of the participants were aware of the term ‘dementia’.Awareness must be spread on dementia and its link with air pollution, especially among elderly people. Awareness must be created on a larger scale of population, and also the public's opinion on dementia and its link with air pollution must be known for further future studies.

Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Sharifa Hasana ◽  
Md. Farhad Hossain ◽  
Md. Siddiqul Islam ◽  
Tapan Behl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Massively Parallel Sequencing ◽  
Late Onset ◽  
Current Knowledge ◽  
The Elderly ◽  
Apoe Ε4 ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

scholarly journals Disease progression modelling from preclinical Alzheimer’s disease (AD) to AD dementia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Soo Hyun Cho ◽  
Sookyoung Woo ◽  
Changsoo Kim ◽  
Hee Jin Kim ◽  
Hyemin Jang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Assessment ◽  
Time Interval ◽  
Disease Course ◽  
Preclinical Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Preclinical Ad ◽  
Cognitive Subscale

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

scholarly journals Changes in retinal microvasculature and retinal layer thickness in association with apolipoprotein E genotype in Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joo Youn Shin ◽  
Eun Young Choi ◽  
Min Kim ◽  
Hyung Keun Lee ◽  
Suk Ho Byeon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Layer Thickness ◽  
Structural Changes ◽  
Foveal Avascular Zone ◽  
Retinal Layer ◽  
Inner Plexiform Layer ◽  
Apoe Ε4 ◽  
Retinal Microvasculature ◽  
Capillary Plexus

AbstractBiomarker tests of Alzheimer’s disease (AD) are invasive and expensive. Recent developments in optical coherence tomography (OCT) and OCT angiography (OCTA) have enabled noninvasive, cost-effective characterization of retinal layer vasculature and thickness. Using OCTA and OCT, we characterized retinal microvascular changes in the mild cognitive impairment (MCI) stage of AD and assessed their correlation with structural changes in each retinal neuronal layer. We also evaluated the effect of the APOE-ε4 genotype on retinal microvasculature and layer thickness. Retinal layer thickness did not differ between MCI patients (40 eyes) and controls (37 eyes, all p > 0.05). MCI patients had lower vessel density (VD) (p = 0.003) of the superficial capillary plexus (SCP) and larger foveal avascular zone area (p = 0.01) of the deep capillary plexus (DCP) than those of controls. VD of the SCP correlated with the ganglion cell layer (r = 0.358, p = 0.03) and inner plexiform layer thickness (r = 0.437, p = 0.007) in MCI patients. APOE-ε4-carrying MCI patients had a lower VD of the DCP than non-carriers (p = 0.03). In conclusion, retinal microvasculature was reduced in patients with AD-associated MCI, but retinal thickness was not changed; these changes might be affected by the APOE genotype. OCTA of the retinal microvasculature may be useful to detect vascular changes in AD.

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