The establishment of a molecular biomarker for early detection of Alzheimer’s disease (AD) is critical for diagnosis and follow up of patients, and as a quantitative parameter in the evaluation of potential new drugs to control AD. A list of blood biomarkers has been reported but none has been validated for the Alzheimer’s clinic. The changes in hyperphosphorylated tau and amyloid peptide in the cerebrospinal fluid is currently used as a tool in the clinics and for research purposes, but this method is highly invasive. Recently, we reported a non-invasive and reliable blood biomarker that correlates the increase in the ratio of heavy tau (HMWtau) and the low molecular weight tau (LMWtau) in human platelets and the decrease in the brain volume as measured by structural MRI. This molecular marker has been named Alz-tau®. Beyond the clinical trials developed with a Latin American population, the present study focuses on an evaluation of this biomarker in a Caucasian population. We examined 36 AD patients and 15 cognitively normal subjects recruited in Barcelona, Spain. Tau levels in platelets were determined by immunoreactivity and the cognitive status by using GDS and MMSE neuropsychological tests. The HMW/LMW tau ratio was statistically different between controls and AD patients. A high correlation was found between the increase in MMSE scores and HMW/LMW tau ratio. This study showed that this ratio is significantly higher in AD patients than controls. Moreover, this study on a peripheral marker of AD is valuable to understanding the AD pathogenesis.
HampelH, SchneiderLS, GiacobiniE, KivipeltoM, SindiS, DuboisB, BroichK, NisticoR, AisenPS, ListaS (2015) Advances in the therapy of Alzheimer’s disease: targeting amyloid beta and tau and perspectives for the future. Expert Rev Neurother15, 83–105.
2.
HebertLE, ScherrPA, BieniasJL, BennettDA, EvansDA (2003) Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol60, 1119–1122.
Mandrekar-ColucciS, LandrethGE (2010) Microglia and inflammation in Alzheimer’s disease. CNS Neurol Disord Drug Targets9, 156–167.
11.
SimicG, Babic LekoM, WrayS, HarringtonC, DelalleI, Jovanov-MilosevicN, BazadonaD, BueeL, de SilvaR, Di GiovanniG, WischikC, HofPR (2016) Tau protein hyperphosphorylation and aggregation in Alzheimer’s disease and other tauopathies, and possible neuroprotective strategies. Biomolecule6, 6.
12.
PozuetaJ, LefortR, ShelanskiML (2013) Synaptic changes in Alzheimer’s disease and its models. Neuroscience251, 51–65.
13.
MaphisN, XuG, Kokiko-CochranON, JiangS, CardonaA, RansohoffRM, LambBT, BhaskarK (2015) Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain138, 1738–1755.
14.
MaphisN, XuG, Kokiko-CochranON, CardonaAE, RansohoffRM, LambBT, BhaskarK (2015) Loss of tau rescues inflammation-mediated neurodegeneration. Front Neurosc9, 196.
15.
CortesN, AndradeV, Guzman-MartinezL, EstrellaM, MaccioniRB (2018) Neuroimmune tau mechanisms: their role in the progression of neuronal degeneration. Int J Mol Sci19, E956.
16.
CortesN, AndradeV, MaccioniRB (2018) Behavioral and neuropsychiatric disorders in Alzheimer’s disease. J Alzheimers Dis63, 899–910.
17.
MaccioniRB, TapiaJP, Guzman-MartinezL (2018) Pathway to tau modifications and the origins of Alzheimer’s disease. Arch Med Res49, 130–131.
SchmandB, HuizengaHM, van GoolWA (2010) Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer’s disease. Psychol Med40, 135–145.
22.
MartinezG, VernooijRW, Fuentes PadillaP, Zamora.J, FlickerL, Bonfill CospX (2017) 18F PET with florbetaben for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev11, CD012883.
23.
ZhangS, SmailagicN, HydeC, Noel-StorrAH, TakwoingiY, McShaneR, FengJ (2014) (11)C-PIB-PET for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev, CD010386.
24.
RojoLE, FernandezJA, MaccioniAA, JimenezJM, MaccioniRB (2008) Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer’s disease. Arch Med Res39, 1–16.
25.
StomrudE, HanssonO, BlennowK, MinthonL, LondosE (2007) Cerebrospinal fluid biomarkers predict decline in subjective cognitive function over 3 years in healthy elderly. Dement Geriatr Cogn Disord24, 118–124.
26.
MaccioniRB, LavadosM, GuillonM, MujicaC, BoschR, FariasG, FuentesP (2006) Anomalously phosphorylated tau and Abeta fragments in the CSF correlates with cognitive impairment in MCI subjects. Neurobiol Aging27, 237–244.
27.
KoyamaA, OkerekeOI, YangT, BlackerD, SelkoeDJ, GrodsteinF (2012) Plasma amyloid-beta as a predictor of dementia and cognitive decline: a systematic review and meta-analysis. Arch Neurol69, 824–831.
28.
FaganAM, MintunMA, ShahAR, AldeaP, RoeCM, MachRH, MarcusD, MorrisJC, HoltzmanDM (2009) Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer’s disease. EMBO Mol Med1, 371–380.
29.
de SouzaLC, ChupinM, LamariF, JardelC, LeclercqD, ColliotO, LehericyS, DuboisB, SarazinM (2012) CSF tau markers are correlated with hippocampal volume in Alzheimer’s disease. Neurobiol Aging33, 1253–1257.
30.
Guzman-MartinezL, FariasGA, MaccioniRB (2013) Tau oligomers as potential targets for Alzheimer’s diagnosis and novel drugs. Front Neurol4, 167.
31.
SlachevskyA, Guzman-MartinezL, DelgadoC, ReyesP, FariasGA, Munoz-NeiraC, BravoE, FariasM, FloresP, GarridoC, BeckerJT, LopezOL, MaccioniRB (2017) Tau platelets correlate with regional brain atrophy in patients with Alzheimer’s disease. J Alzheimers Dis55, 1595–1603.
32.
Guzman-MartinezL, FariasGA, MaccioniRB (2012) Emerging noninvasive biomarkers for early detection of Alzheimer’s disease. Arch Med Res43, 663–666.
33.
FariasG, PerezP, SlachevskyA, MaccioniRB (2012) Platelet tau pattern correlates with cognitive status in Alzheimer’s disease. J Alzheimers Dis31, 65–69.
34.
NeumannK, FariasG, SlachevskyA, PerezP, MaccioniRB (2011) Human platelets tau: a potential peripheral marker for Alzheimer’s disease. J Alzheimers Dis25, 103–109.
35.
BergerZ, RoderH, HannaA, CarlsonA, RangachariV, YueM, WszolekZ, AsheK, Knight.J, DicksonD, AndorferC, RosenberryTL, LewisJ, HuttonM, JanusC (2007) Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J Neurosci27, 3650–3662.
36.
LavadosM, FariasG, RothhammerF, GuillonM, MujicaMC, MaccioniC, MaccioniRB (2005) ApoE alleles and tau markers in patients with different levels of cognitive impairment. Arch Med Res36, 474–479.
