scholarly journals Promise and Challenge: The Lens Model as a Biomarker for Early Diagnosis of Alzheimer's Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Tian Tian ◽  
Boai Zhang ◽  
Yanjie Jia ◽  
Zhaoming Li

Alzheimer’s disease (AD) is the most common form of dementia pathologically characterized by cerebral amyloid-beta (Aβ) deposition. Early and accurate diagnosis of the disease still remains a big challenge. There is evidence that Aβaggregation starts to occur years before symptoms arise. Noninvasive monitoring of Aβplaques is critical for both the early diagnosis and prognosis of AD. Presently, there is a major effort on looking for a reasonably priced technology capable of diagnosing AD by detecting the presence of Aβ. Studies suggest that AD is systemic rather than brain-limited focus diseases and the aggregation of the disease-causing proteins also takes place in lens except the brain. There is a possible relationship between AD and a specific subtype of age-related cataract (supranuclear cataract). If similar abnormal protein deposits are present in the lens, it would facilitate non-invasive diagnosis and monitoring of disease progression. However, there are controversies on the issues related to performance and validation of Aβdeposition in lens as biomarkers for early detection of AD. Here we review the recent findings concerning Aβdeposition in the lenses of AD patients and evaluate if the ocular lens can provide a biomarker for AD.

2002 ◽  
Vol 8 (4) ◽  
pp. 596-597
Author(s):  
Edith V. Sullivan

Alzheimer's disease—occurring upward of 15% of individuals age 65 and older—is the most prevalent age-related dementia. Since the late 1970s, neuropsychologists have been instrumental in identifying patterns of sparing and impairment of cognitive, sensory, and motor functions and rates of declines in selective functions. Anyone who has engaged in longitudinal study of AD and anyone of that large segment of the population with relatives suffering with AD has witnessed first-hand the relentless, irreversible demise of function and ultimate loss of dignity characteristic of AD's course. The approach of Scinto and Daffner's edited book, Early Diagnosis of Alzheimer's Disease, avoids rehashing the already established descriptions of AD and provides firm, scientific rationale for the meaningfulness of early and accurate diagnosis of AD despite its current dire prognosis and lack of effective medical treatment.


2020 ◽  
Vol 31 (8) ◽  
pp. 883-904
Author(s):  
Fidelis Chibhabha ◽  
Yang Yaqi ◽  
Feng Li

AbstractAlzheimer's disease (AD) is a common form of age-related dementia that mostly affects the aging population. Clinically, it is a disease characterized by impaired memory and progressive cognitive decline. Although the pathological hallmarks of AD have been traditionally described with a general confinement in the brain, recent studies have shown similar pathological changes in the retina, which is a developmental outgrowth of the forebrain. These AD-related neurodegenerative changes in the retina have been implicated to cause early visual problems in AD even before cognitive impairment becomes apparent. With recent advances in research, the commonly held view that AD-related cerebral pathology causes visual dysfunction through disruption of central visual pathways has been re-examined. Currently, several studies have already explored how AD manifests in the retina and the possibility of using the same retina as a window to non-invasively examine AD-related pathology in the brain. Non-invasive screening of AD through the retina has the potential to improve on early detection and management of the disease since the majority of AD cases are usually diagnosed very late. The purpose of this review is to provide evidence on the involvement of the retina in AD and to suggest a possible direction for future research into the non-invasive screening, diagnosis, and monitoring of AD using the retina.


Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xavier Hadoux ◽  
Flora Hui ◽  
Jeremiah K. H. Lim ◽  
Colin L. Masters ◽  
Alice Pébay ◽  
...  

Abstract Studies of rodent models of Alzheimer’s disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aβ), may serve as surrogate markers of brain Aβ levels. As Aβ has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aβ. Significant differences in the retinal reflectance spectra are found between individuals with high Aβ burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aβ loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aβ in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aβ load.


Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 913
Author(s):  
Le Minh Tu Phan ◽  
Thi Xoan Hoang ◽  
Thuy Anh Thu Vo ◽  
Jae Young Kim ◽  
Sang-Myung Lee ◽  
...  

Emerging nanomaterials providing benefits in sensitivity, specificity and cost-effectiveness are being widely investigated for biosensors in the application of Alzheimer’s disease (AD) diagnosis. Core biomarkers amyloid-beta (Aβ) and Tau have been considered as key neuropathological hallmarks of AD. However, they did not sufficiently reflect clinical severity and therapeutic response, proving the difficulty of the Aβ- and Tau-targeting therapies in clinical trials. In recent years, there has still been a shortage of sensors for non-Aβ-Tau pathophysiological biomarkers that serve as advanced reporters for the early diagnosis of AD, predict AD progression, and monitor the treatment response. Nanomaterial-based sensors measuring multiple non-Aβ-Tau biomarkers could improve the capacity of AD progression characterization and supervised treatment, facilitating the comprehensive management of AD. This is the first review to principally represent current nanobiosensors for non-Aβ-Tau biomarker and that strategically deliberates future perspectives on the merit of non-Aβ-Tau biomarkers, in combination with Aβ and Tau, for the accurate diagnosis and prognosis of AD.


2020 ◽  
Vol 6 (1) ◽  
pp. 13
Author(s):  
Bhargy Sharma ◽  
Konstantin Pervushin

Drug formulations and suitable methods for their detection play a very crucial role in the development of therapeutics towards degenerative neurological diseases. For diseases such as Alzheimer’s disease, magnetic resonance imaging (MRI) is a non-invasive clinical technique suitable for early diagnosis. In this review, we will discuss the different experimental conditions which can push MRI as the technique of choice and the gold standard for early diagnosis of Alzheimer’s disease. Here, we describe and compare various techniques for administration of nanoparticles targeted to the brain and suitable formulations of nanoparticles for use as magnetically active therapeutic probes in drug delivery targeting the brain. We explore different physiological pathways involved in the transport of such nanoparticles for successful entry in the brain. In our lab, we have used different formulations of iron oxide nanoparticles (IONPs) and protein nanocages as contrast agents in anatomical MRI of an Alzheimer’s disease (AD) brain. We compare these coatings and their benefits to provide the best contrast in addition to biocompatibility properties to be used as sustainable drug-release systems. In the later sections, the contrast enhancement techniques in MRI studies are discussed. Examples of contrast-enhanced imaging using advanced pulse sequences are discussed with the main focus on important studies in the field of neurological diseases. In addition, T1 contrast agents such as gadolinium chelates are compared with the T2 contrast agents mainly made of superparamagnetic inorganic metal nanoparticles.


Nanoscale ◽  
2017 ◽  
Vol 9 (30) ◽  
pp. 10619-10632 ◽  
Author(s):  
Faiz Ul Amin ◽  
Ali Kafash Hoshiar ◽  
Ton Duc Do ◽  
Yeongil Noh ◽  
Shahid Ali Shah ◽  
...  

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.


2021 ◽  
Vol 15 ◽  
Author(s):  
Mengrong Zhang ◽  
Liting Zhong ◽  
Xiu Han ◽  
Guoyin Xiong ◽  
Di Xu ◽  
...  

One of the major challenges in treating Alzheimer's disease (AD) is its early diagnosis. Increasing data from clinical and animal research indicate that the retina may facilitate an early diagnosis of AD. However, a previous study on the 5xFAD (a fast AD model), showing retinal changes before those in the brain, has been questioned because of the involvement of the retinal degeneration allele Pde6brd1. Here, we tested in parallel, at 4 and 6 months of age, both the retinal and the brain structure and function in a 5xFAD mouse line that carries no mutation of rd1. In the three tested regions of the 5xFAD brain (hippocampus, visual cortex, and olfactory bulb), the Aβ plaques were more numerous than in wild-type (WT) littermates already at 4 months, but deterioration in the cognitive behavioral test and long-term potentiation (LTP) lagged behind, showing significant deterioration only at 6 months. Similarly in the retina, structural changes preceded functional decay. At 4 months, the retina was generally normal except for a thicker outer nuclear layer in the middle region than WT. At 6 months, the visual behavior (as seen by an optomotor test) was clearly impaired. While the full-field and pattern electroretinogram (ERG) responses were relatively normal, the light responses of the retinal ganglion cells (measured with multielectrode-array recording) were decreased. Structurally, the retina became abnormally thick with few more Aβ plaques and activated glia cells. In conclusion, the timeline of the degenerative processes in the retina and the brain is similar, supporting the use of non-invasive methods to test the retinal structure and function to reflect changes in the brain for early AD diagnosis.


2019 ◽  
pp. S445-S451 ◽  
Author(s):  
H. Svobodová ◽  
D. Kosnáč ◽  
Z. Balázsiová ◽  
H. Tanila ◽  
P.O. Miettinen ◽  
...  

Iron is very important element for functioning of the brain. Its concentration changes with aging the brain or during disease. The aim of our work was the histological examination of content of ferritin and free iron (unbound) in brain cortex in association with Aβ plaques from their earliest stages of accumulation in amyloid plaque forming APP/PS1 transgenic mice. Light microscopy revealed the onset of plaques formation at 8-monthage. Detectable traces of free iron and no ferritin were found around plaques at this age, while the rate of their accumulation in and around Aβ plaques was elevated at 13 months of age. Ferritin accumulated mainly on the edge of Aβ plaques, while the smaller amount of free iron was observed in the plaque-free tissue, as well as in and around Aβ plaques. We conclude that free iron and ferritin accumulation follows the amyloid plaques formation. Quantification of cortical iron and ferritin content can be an important marker in the diagnosis of Alzheimer’s disease.


2015 ◽  
Vol 44 (2) ◽  
pp. 355-373 ◽  
Author(s):  
Jonathan Stone ◽  
Daniel M. Johnstone ◽  
John Mitrofanis ◽  
Michael O'Rourke

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