TY - JOUR
T1 - Non-Phosphorylated Tau in Cerebrospinal Fluid is a Marker of Alzheimer's Disease Continuum in Young Urbanites Exposed to Air Pollution
AU - Calderón-Garcidueñas, Lilian
AU - Mukherjee, Partha S.
AU - Waniek, Katharina
AU - Holzer, Max
AU - Chao, Chih Kai
AU - Thompson, Charles
AU - Ruiz-Ramos, Rubén
AU - Calderón-Garcidueñas, Ana
AU - Franco-Lira, Maricela
AU - Reynoso-Robles, Rafael
AU - Gónzalez-Maciel, Angélica
AU - Lachmann, Ingolf
N1 - Publisher Copyright:
© 2018 - IOS Press and the authors. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Long-term exposure to fine particulate matter (PM 2.5) and ozone (O 3) above USEPA standards is associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) children exhibit subcortical pretangles in infancy and cortical tau pre-tangles, NFTs, and amyloid phases 1-2 by the 2nd decade. Given their AD continuum, we measured in 507 normal cerebrospinal fluid (CSF) samples (MMC 354, controls 153, 12.82±6.73 y), a high affinity monoclonal non-phosphorylated tau antibody (non-P-Tau), as a potential biomarker of AD and axonal damage. In 81 samples, we also measured total tau (T-Tau), tau phosphorylated at threonine 181 (P-Tau), amyloid-β 1-42, BDNF, and vitamin D. We documented by electron microscopy myelinated axonal size and the pathology associated with combustion-derived nanoparticles (CDNPs) in anterior cingulate cortex white matter in 6 young residents (16.25±3.34 y). Non-P-Tau showed a strong increase with age significantly faster among MMC versus controls (p=0.0055). Aβ 1 - 42 and BDNF concentrations were lower in MMC children (p=0.002 and 0.03, respectively). Anterior cingulate cortex showed a significant decrease (p=<0.0001) in the average axonal size and CDNPs were associated with organelle pathology. Significant age increases in non-P-Tau support tau changes early in a population with axonal pathology and evolving AD hallmarks in the first two decades of life. Non-P-Tau is an early biomarker of axonal damage and potentially valuable to monitor progressive longitudinal changes along with AD multianalyte classical CSF markers. Neuroprotection of young urbanites with PM 2.5 and CDNPs exposures ought to be a public health priority to halt the development of AD in the first two decades of life.
AB - Long-term exposure to fine particulate matter (PM 2.5) and ozone (O 3) above USEPA standards is associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) children exhibit subcortical pretangles in infancy and cortical tau pre-tangles, NFTs, and amyloid phases 1-2 by the 2nd decade. Given their AD continuum, we measured in 507 normal cerebrospinal fluid (CSF) samples (MMC 354, controls 153, 12.82±6.73 y), a high affinity monoclonal non-phosphorylated tau antibody (non-P-Tau), as a potential biomarker of AD and axonal damage. In 81 samples, we also measured total tau (T-Tau), tau phosphorylated at threonine 181 (P-Tau), amyloid-β 1-42, BDNF, and vitamin D. We documented by electron microscopy myelinated axonal size and the pathology associated with combustion-derived nanoparticles (CDNPs) in anterior cingulate cortex white matter in 6 young residents (16.25±3.34 y). Non-P-Tau showed a strong increase with age significantly faster among MMC versus controls (p=0.0055). Aβ 1 - 42 and BDNF concentrations were lower in MMC children (p=0.002 and 0.03, respectively). Anterior cingulate cortex showed a significant decrease (p=<0.0001) in the average axonal size and CDNPs were associated with organelle pathology. Significant age increases in non-P-Tau support tau changes early in a population with axonal pathology and evolving AD hallmarks in the first two decades of life. Non-P-Tau is an early biomarker of axonal damage and potentially valuable to monitor progressive longitudinal changes along with AD multianalyte classical CSF markers. Neuroprotection of young urbanites with PM 2.5 and CDNPs exposures ought to be a public health priority to halt the development of AD in the first two decades of life.
KW - Alzheimer's disease
KW - Aβ 1-42
KW - BDNF
KW - Mexico City
KW - PM 2.5
KW - PrP C
KW - Vitamin D
KW - Wallerian degeneration
KW - air pollution
KW - axonal damage
KW - cerebrospinal fluid
KW - children
KW - combustion-derived nanoparticles
KW - insulin
KW - leptin
KW - non-phosphorylated tau
KW - white matter
UR - http://www.scopus.com/inward/record.url?scp=85058812569&partnerID=8YFLogxK
U2 - 10.3233/JAD-180853
DO - 10.3233/JAD-180853
M3 - Article
C2 - 30412505
AN - SCOPUS:85058812569
SN - 1387-2877
VL - 66
SP - 1437
EP - 1451
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -