Abstract: Exposures to fine particulate matter (PM2.5) and ozone (O3) 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.
Calderón-Garcidueñas L, Vojdani A,Blaurock-Busch E, Busch Y, Friedle A, Franco-Lira M, Sarathi-Mukherjee P, Martínez-Aguirre X, Park SB, Torres-Jardón R, D'Angiulli A.
This important Research, published in the reputable Journal of Alzheimer Disease 2015;43(3):1039-58 demonstrates that combustion metal exposure breaks down the body's natural barriers, including the blood brain barrier.
Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's and adult brains ought to be of pressing importance for public health.
Alzheimer Disease: Mercury as pathogenetic factor and apolipoprotein E as a moderator
The Integration of the Aluminum and Amyloid Cascade Hypotheses
The Alzheimer Disease (AD) Risk factor was up to 5x higher in districts with high aluminium concentration in drinking water.
Other forms of dementia or epilepsy did not show an increased AD risk.
Martin CN et al. Geographical relation between Alzheimer Disease an Aluminium in Drinking Water. The Lancet, Vol 333, Issue 8629, Jan 1989, pp61-62
In addition to several genetic parameters, various environmental factors may influence the risk of getting AD. Blood mercury levels were more than two-fold higher in AD patients as compared to both control groups (p = 0.0005, and p = 0.0000, respectively). In early onset AD patients (n = 13), blood mercury levels were almost three-fold higher as compared to controls (p = 0.0002, and p = 0.0000, respectively). These increases were unrelated to the patients' dental status.
Hock C, Drasch G. Increased blood mercury levels in patients with Alzheimer Disease, Journal of Neural Transmission March 1998, Volume 105, Issue 1, pp 59-68