Exposures to fine particulate matter (PM2.5) and ozone (O3)
above USEPA standards are associated with Alzheimer's disease (AD)
risk. Metropolitan Mexico City (MMC) residents have life time exposures
to PM2.5 and O3 above USEPA standards. We
investigated AD intra and extracellular protein aggregates and
ultrastructural neurovascular pathology in 203 MMC residents age
25.36 ± 9.23 y. Immunohistochemical methods were used to identify AT8
hyperphosphorilated tau (Htau) and 4G8 (amyloid β 17-24). Primary
outcomes: staging of Htau and amyloid, per decade and cumulative PM2.5 (CPM2.5) above standard. Apolipoprotein E allele 4 (APOE4), age and cause of death were secondary outcomes.
above USEPA standards are associated with Alzheimer's disease (AD)
risk. Metropolitan Mexico City (MMC) residents have life time exposures
to PM2.5 and O3 above USEPA standards. We
investigated AD intra and extracellular protein aggregates and
ultrastructural neurovascular pathology in 203 MMC residents age
25.36 ± 9.23 y. Immunohistochemical methods were used to identify AT8
hyperphosphorilated tau (Htau) and 4G8 (amyloid β 17-24). Primary
outcomes: staging of Htau and amyloid, per decade and cumulative PM2.5 (CPM2.5) above standard. Apolipoprotein E allele 4 (APOE4), age and cause of death were secondary outcomes.
Subcortical
pretangle stage b was identified in an 11month old baby. Cortical tau
pre-tangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases
1–2, Htau in substantia nigrae, auditory, oculomotor, trigeminal and
autonomic systems were identified by the 2nd decade. Progression to NFT
stages III-V was present in 24.8% of 30–40 y old subjects. APOE4
carriers have 4.92 times higher suicide odds (p = 0.0006), and 23.6
times higher odds of NFT V (p < 0.0001) v APOE4 non-carriers having
similar CPM2.5 exposure and age. Age (p = 0.0062) and CPM2.5 (p = 0.0178) were significant for developing NFT V. Combustion-derived nanoparticles
were associated with early and progressive damage to the neurovascular
unit. Alzheimer's disease starting in the brainstem of young children
and affecting 99.5% of young urbanites is a serious health crisis. Air pollution control
should be prioritised. Childhood relentless Htau makes a fundamental
target for neuroprotective interventions and the first two decades are
critical. We recommend the concept of preclinical AD be revised and
emphasize the need to define paediatric environmental, nutritional,
metabolic and genetic risk factor interactions of paramount importance
to prevent AD. AD evolving from childhood is threating the wellbeing of
our children and future generations.
pretangle stage b was identified in an 11month old baby. Cortical tau
pre-tangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases
1–2, Htau in substantia nigrae, auditory, oculomotor, trigeminal and
autonomic systems were identified by the 2nd decade. Progression to NFT
stages III-V was present in 24.8% of 30–40 y old subjects. APOE4
carriers have 4.92 times higher suicide odds (p = 0.0006), and 23.6
times higher odds of NFT V (p < 0.0001) v APOE4 non-carriers having
similar CPM2.5 exposure and age. Age (p = 0.0062) and CPM2.5 (p = 0.0178) were significant for developing NFT V. Combustion-derived nanoparticles
were associated with early and progressive damage to the neurovascular
unit. Alzheimer's disease starting in the brainstem of young children
and affecting 99.5% of young urbanites is a serious health crisis. Air pollution control
should be prioritised. Childhood relentless Htau makes a fundamental
target for neuroprotective interventions and the first two decades are
critical. We recommend the concept of preclinical AD be revised and
emphasize the need to define paediatric environmental, nutritional,
metabolic and genetic risk factor interactions of paramount importance
to prevent AD. AD evolving from childhood is threating the wellbeing of
our children and future generations.
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