Lipid Biomarkers in Alzheimer's Disease

Abstract

There are now several lines of evidence that lipids play fundamental roles in the pathogenesis of AD and that some of them have a prognostic and diagnosis value. This may pave the way for the identification of new therapeutic targets, new effective drugs and / or new treatments.

Targeted Lipidomics Investigation of N‐acylethanolamines in a Transgenic Mouse Model of AD: A Longitudinal Study

“…Moreover, non‐esterified monounsaturated fatty acids (MUFA), as well as their biosynthetic enzyme stearoyl‐CoA desaturase, are elevated in the cortex and hippocampus and reduced in the plasma of AD patients . Finally, lipidomics analysis provided evidence for alterations in lipid profiles in AD brain areas, cerebrospinal fluid and blood …”

Structural basis of GIRK2 channel modulation by cholesterol and PIP2

“…For example, hypercholesterolemia causes impairment of dopamine signaling and psychomotor dysfunction in mice [45][46][47][48] . Increases in cholesterol levels have been shown to elevate beta-amyloid precursor protein levels in cholesterol-enriched lipid rafts 49 and are associated with increased risk for AD 50 . Accordingly, there is a growing need to understand how cholesterol affects brain function.…”

Advance of sporadic Alzheimer's disease animal models

“…The cholinergic system is involved in critical physiological processes, such as attention, learning, memory, stress response, wakefulness and sleep, and sensory information. While an extensive loss of forebrain cholinergic neurons accompanied by a reduction of the cholinergic fiber network were found in the cortical mantel and hippocampus of AD patients 15,16 Gut microbiota Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration 17,18 Lipid metabolism abnormalities Cholesterol metabolic abnormalities could accelerate the formation of Aβ and phosphorylated Tau protein, oxidative stress, neuronal apoptosis, and microglial activation 19,20 Autophagy dysfunction Autophagy has a pivotal role in the disposal of Aβ and Tau aggregates. The reduction of Akt signaling redeems GSK3β from inhibition which in addition to causing Tau phosphorylation and aggregation, it disrupts autophagy signaling thus reducing the clearance of amyloid precursor 21,22 Insulin resistance state Brain glucose deficit showed significant memory impairments, reduction of synaptic long-term potentiation, increased Tau phosphorylation, Aβ deposition, and loss of neurons 3 Synapse dysfunction The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss 9,23 Metal ions disorder The dysfunction of metal ions can promote the development of pathological changes, leading to the accumulation of misfolded Aβ and phosphorylated Tau protein, oxidative stress, and DNA oxidative damage 24,25 Abbreviations: Aβ, β-amyloid; AD, Alzheimer's disease; IL, interleukin; GSK3, glycogen synthase kinase 3β; ROS, reactive oxygen species; TNF-α, tumour necrosis factor α.…”

“…While nearly 95% of patients with AD are classified as sAD, which are caused by a combination of genetic factors and environmental risk factors without documented familial history of AD . Various hypotheses of mechanisms for sAD include deposition of β‐amyloid (Aβ), hyperphosphorylation of Tau, oxidative stress, neuroinflammation, cholinergic neuron degeneration, gut microbiota disorders, lipid metabolism abnormalities, autophagy dysfunction, insulin desensitization/resistance state, synapse dysfunction, and metal ions disorders in the brain (summarized in Table ).…”