Perspective Insights into Disease Progression, Diagnostics, and Therapeutic Approaches in Alzheimer's Disease: A Judicious Update

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and−2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication. Cellular stress that arises through mitochondrial dysfunction, endoplasmic reticulum malfunction, and autophagy contributes significantly to the pathogenesis of AD. With high accuracy in disease diagnostics, Aβ deposition and phosphorylated tau (p-tau) are useful core biomarkers in the cerebrospinal fluid (CSF) of AD patients. Although five drugs are approved for treatment in AD, their failures in achieving complete disease cure has shifted studies toward a series of molecules capable of acting against Aβ and p-tau. Failure of biologics or compounds to cross the blood-brain barrier (BBB) in most cases advocates development of an efficient drug delivery system. Though liposomes and polymeric nanoparticles are widely adopted for drug delivery modules, their use in delivering drugs across the BBB has been overtaken by exosomes, owing to their promising results in reducing disease progression.

Age‐related deterioration of motor function in male and female 5xFAD mice from 3 to 16 months of age

“…After 12 months of age, however, 5xFAD mice frequently showed abnormal clasping of the hind-limbs when suspended by the tail, 22,24 and often showed an abnormal hunched posture, poor coat condition, and in rare cases, prolapsis of the penis, all of which are indicative of impaired neuromuscular function. The 5xFAD and WT mice did not differ in body weight at either 3 or 6 months of age ( Figure 1), but the 5xFAD mice weighed less than WT mice at 9 (F (1,50) = 7.16, P = 0.01), 12 (F (1,44) = 8.06, P < 0.05) and 15 months of age (F (1,41) = 31.20, P < 0.0001).…”

“…There were significant sex differences at each age, as males consistently weighed more than females (P < 0.0001). There was also a genotype by sex interaction at 12 months of age (F (1,44)…”

“…Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by the development of Aβ‐plaques, neurofibrillary tangles and cognitive dysfunction . Motor dysfunction also develops in AD, and manifests as altered gait, hyperactivity and motor stereotypes .…”

“…Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the development of Aβ-plaques, neurofibrillary tangles and cognitive dysfunction. [1][2][3][4][5] Motor dysfunction also develops in AD, and manifests as altered gait, hyperactivity and motor stereotypes. [6][7][8][9] There is an increasing understanding that motor impairments contribute to overall AD severity, and that there is a need for ameliorating these impairments.…”

Potential therapeutics of Alzheimer's diseases: New insights into the neuroprotective role of trehalose‐conjugated beta sheet breaker peptides

“…Unlike other human pathologies, AD has so far proved to be extraordinarily refractory to any attempt aimed at halting or slowing the progression of the disease. Indeed, current approved drugs provide some relief of the AD symptoms, but do not contrast the causes of disease neither delay its progression . Therefore, the identification of pharmacologically effective targets is urgently needed for AD.…”