Atrophy of Basal Forebrain Initiates with Tau Pathology in Individuals at Risk for Alzheimer's Disease
Por:
Cantero, JL, Atienza, M, Lage, C, Zaborszky, L, Vilaplana, E, Lopez-Garcia, S, Pozueta, A, Rodriguez-Rodriguez, E, Blesa, R, Alcolea, D, Lleo, A, Sanchez-Juan, P, Fortea, J, Alzheimers Dis Neuroimaging Initia
Publicada:
1 abr 2020
Resumen:
Evidence suggests that the basal forebrain (BF) cholinergic system degenerates early in the course of Alzheimer's disease (AD), likely due to the vulnerability of BF cholinergic neurons to tau pathology. However, it remains unclear whether the presence of tauopathy is the only requirement for initiating the BF degeneration in asymptomatic subjects at risk for AD (AR-AD), and how BF structural deficits evolve from normal aging to preclinical and prodromal AD. Here, we provide human in vivo magnetic resonance imaging evidence supporting that abnormal cerebrospinal fluid levels of phosphorylated tau (T+) are selectively associated with bilateral volume loss of the nucleus basalis of Meynert (nbM, Ch4) in AR-AD individuals. Spreading of atrophy to medial septum and vertical limb of diagonal band Broca (Ch1-Ch2) occurred in both preclinical and prodromal AD. With the exception of A+, all groups revealed significant correlations between volume reduction of BF cholinergic compartments and atrophy of their innervated regions. Overall, these results support the central role played by tauopathy in instigating the nbM degeneration in AR-AD individuals and the necessary coexistence of both AD proteinopathies for spreading damage to larger BF territories, thus affecting the core of the BF cholinergic projection system.
Filiaciones:
Cantero, JL:
Pablo de Olavide Univ, Lab Funct Neurosci, Ctra Utrera Km 1, Seville 41013, Spain
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Atienza, M:
Pablo de Olavide Univ, Lab Funct Neurosci, Ctra Utrera Km 1, Seville 41013, Spain
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Lage, C:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Cantabria, Univ Hosp Marques de Valdecilla, Serv Neurol, IDIVAL, Santander 39008, Spain
Zaborszky, L:
Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA
Vilaplana, E:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp Santa Creu & St Pa, Dept Neurol, Barcelona 08025, Spain
Lopez-Garcia, S:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Cantabria, Univ Hosp Marques de Valdecilla, Serv Neurol, IDIVAL, Santander 39008, Spain
Pozueta, A:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Cantabria, Univ Hosp Marques de Valdecilla, Serv Neurol, IDIVAL, Santander 39008, Spain
Rodriguez-Rodriguez, E:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Cantabria, Univ Hosp Marques de Valdecilla, Serv Neurol, IDIVAL, Santander 39008, Spain
Blesa, R:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp Santa Creu & St Pa, Dept Neurol, Barcelona 08025, Spain
Alcolea, D:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp Santa Creu & St Pa, Dept Neurol, Barcelona 08025, Spain
Lleo, A:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp Santa Creu & St Pa, Dept Neurol, Barcelona 08025, Spain
Sanchez-Juan, P:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Cantabria, Univ Hosp Marques de Valdecilla, Serv Neurol, IDIVAL, Santander 39008, Spain
Fortea, J:
CIBERNED, Network Ctr Biomed Res Neurodegenerat Dis, Madrid 28031, Spain
Univ Autonoma Barcelona, Inst Invest Biomed St Pau Hosp Santa Creu & St Pa, Dept Neurol, Barcelona 08025, Spain
Green Published
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