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laboratory evaluation of Alzheimer's disease

Laboratory: === routine === 1) thyroid function tests 2) erythrocyte sedimentation rate (ESR) or serum C-reactive protein (serum CRP) 3) chemistry panel a) serum electrolytes b) serum glucose c) renal function tests d) liver function tests 4) urinalysis 5) complete blood count (CBC) 6) serum vitamin B12 (likely unhelpful [11]) & serum folate 7) serologic test for syphilis (not routinely indicated) 8) Tropheryma whipplei DNA (if diarrhea) 9) HIV1 serology === CSF analysis (lumbar puncture) (not routinely indicated) === - slow virus - fungal disease - CSF Abeta42 - earliest marker of AD [12] - CSF Abeta42 decreased in spontaneous cerebral amyloid angiopathy vs AD [31] - CSF phospho-tau (microtubule-associated protein tau) - CSF beta-amyloid & CSF phospho-tau positive characterizes AD - 73% of CSF beta-amyloid positive & CSF phospho-tau negative patients show pathologic changes of AD [28] - ratio of CSF Abeta [1-42] / CSF phospho-Thr-181-tau & total CSF tau [3] predicts elderly with MCI likely to progress to AD [10] - VSNL1 is increased in CSF of AD patients - CSF neurogranin is elevated in patients with Alzheimer disease & to a lesser extent mild cognitive impairment [22] - tau in CSF + amyloid-beta 42 in CSF in addition to brain MRI proposed to predict progression of mild cognitive impairment to Alzheimer's disease [16] - phosphorylated tau in CSF - N-terminal phospho-tau181 in CSF & N-terminal phospho-tau217 in CSF with concordance of 88.2%, better than mid phospho-tau181 in CSF with either N-terminal measure [25] === serum/plasma biomarkers of Alzheimer's disease === - phosphorylated tau in serum/plasma - phosphorylated tau181 in serum distingishes AD from FTD [21] - phosphorylated tau217 in plasma able to discriminate Alzheimer disease from other neurodegenerative diseases [23] - plasma phospho-tau combined with executive function & memory tests useful for prediction of Alzheimer's disease among older persons with memory complaints [26] - higher plasma p-tau181 predict faster decline in most cognitive, physical, & functional outcomes[40] - amyloid-beta in plasma proposed as screening tool [17] - plasma APP/Abeta [1-42] & plasma Abeta40/42 - plasma Abeta42/40 best predicts brain amyloidosis in blacks & non-Hispanic whites [29] - lower Abeta42/40 predict faster declines in verbal episodic memory & semantic fluency performance [40] - amyloid probability score 2 (APS2) is an alorithm using plasma ptau217/total tau + plasma amyloid-beta 42/40 in the diagnostic workup of Alzheimer's disease [41] - no difference in diagnostic accuracy between APS2 & plasma ptau217 alone [41] - neurofilament light chain in serum/plasma levels (plasma NfL) correspond with hallmarks of Alzheimer's disease progression - higher plasma NfL predict faster decline in global cognition, semantic fluency, verbal episodic memory, & activities of daily living [40] - plasma GFAP - outperforms CSF GFAP in predicting amyloid-beta pathology in early Alzheimer's disease [27] - appears earlier in plasma than plasma phosphorylated tau181 or plasma neurofilament light chain [30] - higher plasma Abeta40/42, ptau181, plasma NfL, & plasma GFAP are associated with higher risk for cardiovascular disease, mortality from heart failure & kidney disease - plasma biomarkers of Alzheimer's disease differ by sex & comorbidities [34] - phosphorylated plasma amyloid-beta 42/40 - plasma phosphorylated tau181 (plasma p-tau181) M > F - chronic kidney disease associated with higher plasma p-tau181 - higher plasma p-tau181 associated with lower MMSE scores - plasma glial fibrillary acidic protein (plasma GFAP) F > M, - diabetes & higher BMI associated with lower plasma GFAP - higher plasma GFAP associated with lower MMSE scores - plasma neurofilament light chain (plasma NfL) - higher BMI associated with lower plasma NfL - stroke associated with higher plasma NfL [34] - plasma exosome neurogranin is diminished in patients with Alzheimer disease & mild cognitive impairment [22] - serum antibodies to beta amyloid & RAGE may be increased in patients with Alzheimer's disease [5] - serum IL6 may be increased [11] - biomarkers not cost effective in the absence of disease modifying therapy [14] - blood biomarker tests for amyloid pathology are more acceptable, accessible & scalable than amyloid PET or CSF tests [38] - plasma p-tau217 outperforms plasma p-tau181 & plasma p-tau231 & other plasma biomarkers of Alzheimer's disease in identifying which patients may benefit from an anti-beta-amyloid anti-Alzheimer monoclonal antibody [39] === proteomics === - battery of 18 plasma proteins [9] including: - ANG-2, CCL5/RANTES, CCL7/MCP-3, CCL15, CCL18, CXCL8/IL-8, EGF, G-CSF, GDNF, ICAM-1, IGFBP-6, IL-1a, IL-3, IL-11, M-CSF, PDGF-BB, TNF-alpha - 32 dementia-associated plasma proteins are involved in proteostasis, immunity, synaptic function, & extracellular matrix organization [33] - 12 of these 32 are associated with CSF biomarkers of AD, neurodegeneration, or neuroinflammation - SERPINA3 - some of the proteins most strongly associated with risk of dementia, are not detected in brain tissue - GDF15 - five different subtypes of AD identified by CSF proteomics of 1038 proteins [37] - type 1: characterized by proteins related to neuronal hyperplasticity - enriched with TREM2 R47H - longest average survival time 8.9 years - increased CSF total-tau & CSF p-tau - type 2: characterized by innate immune activation - increased CSF total-tau & CSF p-tau - along with subtype 5, highest risk of MCI progression to dementia - type 3: characterized by RNA dysregulation - shortest average survival time 5.6 years - increased CSF total-tau & CSF p-tau - type 4: characterized by choroid plexus dysfunction - normal CSF total-tau & CSF p-tau (relative to controls) - lowest risk of MCI progression to dementia - type 5: characterized by blood-brain barrier dysfunction [37] - normal CSF total-tau & CSF p-tau (relative to controls) - along with subtype 2, highest risk of MCI progression to dementia === lipids === - serum cholesterol, serum LDL, serum HDL NOT risk factors [1] - serum cholesterol-ester DHA levels may correlate with severity of dementia [2] - a set of ten lipids depleted in peripheral blood predict mild cognitive impairment or Alzheimer's disease within a 2-3 year period (90% accuracy) [13] - set includes 8 phosphatidylcholines & 2 acylcarnitines - set of 10 relects membrane integrity [13] === other body fluids === - salivary/buccal specimens - phosphorylated tau in buccal swab (AAD meeting abstract) - salivary Abeta42 proposed as a screening test - soluble Abeta oligomers, a 12-mer Abeta*56 & a 15-mer AbetaO are elevated in nasal secretions of patients with Alzheimer's disease [24] - higher 12-mer Abeta*56 in mild AD & higher 15-mer AbetaO in moderate AD - urine tests for neural thread protein* & for isoprostane 8,12-iso-iPf2alpha-VI may possibly be useful [6] - did not get FDA approval in 2005 [8] === genetic testing === - presenilin 1 mutation [4] - apo-E4 genotype more common in blacks than whites [34] - do not order apoE genotyping in patients with suspected AD [14] === investigational === - attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) may eventually have a role in diagnosis [15] - DNA aptamer-attached portable graphene biosensor - detects beta-amyloid, microtubule-associated protein tau, & alpha-synuclein in easily accessible biofluids [35] === direct-to-consumer Alzheimer testing === - also see direct-to-consumer Alzheimer testing

Related

Alzheimer's disease (AD) clinical laboratory test direct-to-consumer Alzheimer testing (Quest AD-Detect test) intestinal lipodystrophy (Whipple's disease)

Specific

CSF proteomic analysis of Alzheimer's disease subtypes PrecivityAD2 blood test algorithm; amyloid probability score 2 (APS2); plasma ptau217/total tau + amyloid-beta-42/amyloid-beta-40 in plasma

General

laboratory analysis

References

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