Lipids as Early and Minimally Invasive Biomarkers for Alzheimer’s Disease

Abstract

: Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Specifically, typical late-onset AD is a sporadic form with a complex etiology that affects over 90% of patients. The current gold standard for AD diagnosis is based on the determination of amyloid status by the analysis of cerebrospinal fluid samples or by brain positron emission tomography. These procedures have some disadvantages to become widely used (expensive, invasive). As alternative, blood metabolites have recently emerged as promising AD biomarkers. Small molecules that cross the compromised AD blood-brain barrier, could be determined in plasma to improve clinical AD diagnosis at early stages through minimally invasive techniques. Specifically, lipids could play an important role in AD since brain has a high lipid content and they are present ubiquitously inside amyloid plaques. Therefore, a systematic review was performed with the aim of identifying blood lipid metabolites as potential early AD biomarkers. In conclusion, some lipid families (fatty acids, glycerolipids, glycerophospholipids, sphingolipids, lipid peroxidation compounds) showed impaired levels at early AD stages. Ceramide levels were significantly higher in AD subjects and polyunsaturated fatty acids levels were significantly lower in AD. Also, high arachidonic acid levels were found in AD patients in contrast to low sphingomyelin levels. Consequently, these lipid biomarkers could be used for minimally invasive and early AD clinical diagnosis.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…Lipids constitute around 50% of dry brain weight and they exert key roles in basic brain functions, such as blood–brain barrier (BBB) integrity, myelination, vesicle trafficking, APP processing, and neuroinflammation [ 294 , 295 ]. Since alterations in these processes have been implicated in the pathophysiology of several brain disorders, including AD, a proposal has been made for their use as markers [ 296 ]. However, standard imaging methods (i.e., PET or MRI) are not suitable for lipid detection, and brain biopsies remain inapplicable, thus leaving the CSF as a potential source of biomarkers [ 297 , 298 ].…”

Advances and applications of fluids biomarkers in diagnosis and therapeutic targets of Alzheimer's disease

“…However, since the pathological phenomenon behind microvascular damage is not fully established in AD and could only be a secondary lesion in the late stage, its significance as a biomarker for early diagnosis may be minimal 96 . Similar changes occur in many neurological diseases, and the specificity is not high in AD, even though lipid metabolites may be a new direction 135 . Thus, the possibility of utilizing them as early diagnostic markers for AD is doubtful.…”

“… 96 Similar changes occur in many neurological diseases, and the specificity is not high in AD, even though lipid metabolites may be a new direction. 135 Thus, the possibility of utilizing them as early diagnostic markers for AD is doubtful. MiRNA has been a hot area recently since its length is too short and its nucleotide sequences are not specific.…”

Relationship between Plasma Lipid Profile and Cognitive Status in Early Alzheimer Disease

“…Also, a colocalization of lipids (e.g., cholesterol, ApoE) and amyloid plaques was observed in some studies [19,20]. Therefore, there is an increasing interest in the determination of lipids in different biological fluids (e.g., CSF, plasma) as potential AD biomarkers [21,22]. Some lipid panels have been postulated as potential biomarkers for the diagnosis and prediction of cognitive decline [23][24][25].…”