Early neurotransmission impairment in non-invasive Alzheimer Disease detection

Peña-Bautista, Carmen; Torres-Cuevas, Isabel; Baquero, Miguel; Ferrer, I.; Garcı́a, Lorena; Vento, Máximo; Cháfer-Pericás, Consuelo

doi:10.1038/s41598-020-73362-z

Cited by 16 publications

(9 citation statements)

References 53 publications

(48 reference statements)

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“…On the contrary, ACh levels in the submandibular gland from AD patients were found higher compared with control subjects (p < 0.05; Figure 4B ), in agreement with previously reported data in saliva ( 33 ). These findings may be explained by the use of acetylcholinesterase (AChE) inhibitors in the treatment of AD, which may help to increase and prolong the activity period of the released Ach.…”

Section: Resultssupporting

confidence: 93%

“…In agreement with this, AChE activity was found significantly lower in AD patients compared with healthy control age-matched subjects ( 34 ). Moreover, a recent study showed higher levels of ACh in saliva from AD patients ( 33 ). In our present study, 13 out of 15 AD patients were under AchE inhibitor treatment, which could explain the higher Ach levels observed in their submandibular glands.…”

Section: Discussionmentioning

confidence: 99%

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Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease

et al. 2021

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In the last few years, microbial infection and innate immune theories have been proposed as an alternative approach explaining the etiopathogenesis and origin of Alzheimer’s disease (AD). Lactoferrin, one of the main antimicrobial proteins in saliva, is an important modulator of immune response and inflammation, and represents an important defensive element by inducing a broad spectrum of antimicrobial effects against microbial infections. We demonstrated that lactoferrin levels in saliva are decreased in prodromal and dementia stages of AD compared with healthy subjects. That finding seems to be specific to cerebral amyloid-β (Aβ) load as such observation was not observed in healthy elderly controls or those subjects with frontotemporal dementia. In the present study, we analysed salivary lactoferrin levels in a mouse model of AD. We observed robust and early reduction of lactoferrin levels in saliva from 6- and 12-month-old APP/PS1 mice. Because saliva is secreted by salivary glands, we presume that deregulation in salivary glands resulting in reduced salivary lactoferrin levels may occur in AD. To test this hypothesis, we collected submandibular glands from APP/PS1 mice, as well as submandibular gland tissue from AD patients and we analysed the expression levels of key components of the salivary protein signalling pathway. A significant reduction in M3 receptor levels was found along with decreased acetylcholine (Ach) levels in submandibular glands from APP/PS1 mice. Similarly, a reduction in M3 receptor levels was observed in human submandibular glands from AD patients but in that case, the Ach levels were found increased. Our data suggest that the ACh-mediated M3 signalling pathway is impaired in salivary glands in AD, resulting in salivary gland dysfunction and reduced salivary lactoferrin secretion.

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease

et al. 2021

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“…[ 1,2 ] Suitable methods used to diagnose an individual's predisposition toward neurological degeneration and dementia‐associated disorders through early biomarkers can bridge this gap. [ 3–5 ] The worldwide social and economic impact of Alzheimer's disease (AD) dictates the need for the timely invention of theranostics (therapeutics + diagnostics) for this disease. Continuous failure of anti‐AD drugs targeted to neurotransmitters and their interactions with toxic amyloid‐β (Aβ) peptides in clinical trials has brought the spotlight back to amyloidosis in AD.…”

Section: Introductionmentioning

confidence: 99%

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

Sharma

Grandjean

Phillips

et al. 2021

Advanced NanoBiomed Research

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With a significant proportion of the global population growing older (>60 years), the low success rates of current diagnoses for early neurodegeneration signs are disappointing. Early detection of Alzheimer's disease (AD) can improve acclimatization and quality of life for patients in their later years. Endogenous proteins, such as the most abundant secreted protein in cerebrospinal fluid, lipocalin‐type prostaglandin d synthase (L‐PGDS), can bind the early toxic oligomers of amyloid β (Aβ) peptides implicated in AD and prevent their aggregation. Herein, the utility of L‐PGDS for detection of amyloids is demonstrated. L‐PGDS is conjugated with different iron‐oxide magnetic nanoparticles for contrast‐enhanced visualization using magnetic resonance imaging (MRI). These conjugates inhibit amyloid aggregation in vitro and improve viability in neuronal cells incubated with amyloid fibrils, showing a potential neuroprotective function. L‐PGDS‐ferritin conjugates, when administered intraventricularly, localize to AD‐associated amyloid‐rich regions in mice brain imaged using MRI and histological stains. As a proof‐of‐concept, it is demonstrated that L‐PGDS conjugates could reach the brain regions through non‐invasive intranasal administration. These conjugates are developed as the first entirely protein‐based nanoprobes for early detection of brain amyloids. The results of this study open a wider avenue for study of endogenous proteins as potential theranostics for AD.

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“…Furthermore, a multivariate analysis including sensitivity, specificity and area under the curve (AUC) revealed a few promising indices for creatine, acetylcholine, glutamine and myo-inositol. These neurotransmitters could be used as promising non-invasive biomarkers for diagnosing AD and cognitive impairment [ 57 ].…”

Section: Biomarkers In the Diagnosis Of Alzheimer’s Diseasementioning

confidence: 99%

The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Pawlik

Błochowiak

2021

Diagnostics

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Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

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Early neurotransmission impairment in non-invasive Alzheimer Disease detection

Cited by 16 publications

References 53 publications

Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease

Salivary Lactoferrin Expression in a Mouse Model of Alzheimer’s Disease

Lipocalin‐Type Prostaglandin d Synthase Conjugates as Magnetic Resonance Imaging Contrast Agents for Detecting Amyloid β‐Rich Regions in the Brain of Live Alzheimer's Disease Mice

The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

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