Early Diagnosis of Alzheimer’s Disease: Moving Toward a Blood-Based Biomarkers Era

Tao, Qing‐Qing; Lin, Ru; Wu, Zhi‐Ying

doi:10.2147/cia.s394821

Cited by 4 publications

(2 citation statements)

References 43 publications

(47 reference statements)

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“…AD pathology is divided into three distinct phases: preclinical, prodromal with associated mild cognitive impairment (MCI), and a distinctive dementia phase. In individuals with MCI, altered brain imaging and cerebrospinal fluid biomarkers have been linked to progression to dementia [ 3 ]. Once the dementia stage is reached, existing treatments can delay but cannot halt the disease progression.…”

Section: Introductionmentioning

confidence: 99%

Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice

Rombaut,

Schepers,

Tiane

et al. 2024

Cells

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Microglia activity can drive excessive synaptic loss during the prodromal phase of Alzheimer’s disease (AD) and is associated with lowered cyclic adenosine monophosphate (cAMP) due to cAMP phosphodiesterase 4B (PDE4B). This study aimed to investigate whether long-term inhibition of PDE4B by A33 (3 mg/kg/day) can prevent synapse loss and its associated cognitive decline in APPswe/PS1dE9 mice. This model is characterized by a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9 (dE9), both under the control of the mouse prion protein promoter. The effects on cognitive function of prolonged A33 treatment from 20 days to 4 months of age, was assessed at 7–8 months. PDE4B inhibition significantly improved both the working and spatial memory of APPswe/PSdE9 mice after treatment ended. At the cellular level, in vitro inhibition of PDE4B induced microglial filopodia formation, suggesting that regulation of PDE4B activity can counteract microglia activation. Further research is needed to investigate if this could prevent microglia from adopting their ‘disease-associated microglia (DAM)’ phenotype in vivo. These findings support the possibility that PDE4B is a potential target in combating AD pathology and that early intervention using A33 may be a promising treatment strategy for AD.

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Section: Introductionmentioning

confidence: 99%

Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice

Rombaut,

Schepers,

Tiane

et al. 2024

Cells

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show abstract

“…More recently, early-stage indicators such as imaging-based and fluid biomarkers have shown great potential for early detection of AD [6]. Fluid biomarkers found in blood and CSF have now become standard methods of diagnosing early AD patients [7][8][9], even showing great potential for subtyping AD [10]. Similarly, recent imaging-based approaches such as brain connectivity analysis in the form of connectomes have shown promising results for early diagnosis [11].…”

Section: Introductionmentioning

confidence: 99%

Identifying Progression-Specific Alzheimer’s Subtypes Using Multimodal Transformer

Machado Reyes,

Chao,

Hahn

et al. 2024

JPM

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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, yet its current treatments are limited to stopping disease progression. Moreover, the effectiveness of these treatments remains uncertain due to the heterogeneity of the disease. Therefore, it is essential to identify disease subtypes at a very early stage. Current data-driven approaches can be used to classify subtypes during later stages of AD or related disorders, but making predictions in the asymptomatic or prodromal stage is challenging. Furthermore, the classifications of most existing models lack explainability, and these models rely solely on a single modality for assessment, limiting the scope of their analysis. Thus, we propose a multimodal framework that utilizes early-stage indicators, including imaging, genetics, and clinical assessments, to classify AD patients into progression-specific subtypes at an early stage. In our framework, we introduce a tri-modal co-attention mechanism (Tri-COAT) to explicitly capture cross-modal feature associations. Data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (slow progressing = 177, intermediate = 302, and fast = 15) were used to train and evaluate Tri-COAT using a 10-fold stratified cross-testing approach. Our proposed model outperforms baseline models and sheds light on essential associations across multimodal features supported by known biological mechanisms. The multimodal design behind Tri-COAT allows it to achieve the highest classification area under the receiver operating characteristic curve while simultaneously providing interpretability to the model predictions through the co-attention mechanism.

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Alzheimer’s disease: a review on the current trends of the effective diagnosis and therapeutics

Abdul Manap,

Almadodi,

Sultana

et al. 2024

Front. Aging Neurosci.

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The most prevalent cause of dementia is Alzheimer’s disease. Cognitive decline and accelerating memory loss characterize it. Alzheimer’s disease advances sequentially, starting with preclinical stages, followed by mild cognitive and/or behavioral impairment, and ultimately leading to Alzheimer’s disease dementia. In recent years, healthcare providers have been advised to make an earlier diagnosis of Alzheimer’s, prior to individuals developing Alzheimer’s disease dementia. Regrettably, the identification of early-stage Alzheimer’s disease in clinical settings can be arduous due to the tendency of patients and healthcare providers to disregard symptoms as typical signs of aging. Therefore, accurate and prompt diagnosis of Alzheimer’s disease is essential in order to facilitate the development of disease-modifying and secondary preventive therapies prior to the onset of symptoms. There has been a notable shift in the goal of the diagnosis process, transitioning from merely confirming the presence of symptomatic AD to recognizing the illness in its early, asymptomatic phases. Understanding the evolution of disease-modifying therapies and putting effective diagnostic and therapeutic management into practice requires an understanding of this concept. The outcomes of this study will enhance in-depth knowledge of the current status of Alzheimer’s disease’s diagnosis and treatment, justifying the necessity for the quest for potential novel biomarkers that can contribute to determining the stage of the disease, particularly in its earliest stages. Interestingly, latest clinical trial status on pharmacological agents, the nonpharmacological treatments such as behavior modification, exercise, and cognitive training as well as alternative approach on phytochemicals as neuroprotective agents have been covered in detailed.

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Early Diagnosis of Alzheimer’s Disease: Moving Toward a Blood-Based Biomarkers Era

Cited by 4 publications

References 43 publications

Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice

Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice

Identifying Progression-Specific Alzheimer’s Subtypes Using Multimodal Transformer

Alzheimer’s disease: a review on the current trends of the effective diagnosis and therapeutics

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