X-Message-Number: 30766
Date: Sun, 25 May 2008 21:25:32 -0700 (PDT)
From: 
Subject: A possible research direction for AmyloSENS

http://www.mfoundation.org/index.php?pagename=amylosens

Ann Neurol. 2008 Mar 21;63(5):591-601. [Epub ahead of print] A nasal
proteosome adjuvant activates microglia and prevents amyloid deposition.
    Frenkel D, Puckett L, Petrovic S, Xia W, Chen G, Vega J,
Dembinsky-Vaknin A, Shen J, Plante M, Burt DS, Weiner HL. Center for
Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA.
    OBJECTIVE: We assessed whether peripheral activation of microglia by
a nasal proteosome-based adjuvant (Protollin) that has been given safely
to humans can prevent amyloid deposition in young mice and affect amyloid
deposition and memory function in old mice with a large amyloid load.
METHODS: Amyloid precursor protein (APP) transgenic (Tg) J20 mice
received nasal treatment with Protollin weekly for 8 months beginning at
age 5 months. Twenty-four-month-old J20 mice were treated weekly for 6
weeks. RESULTS: We found reduction in the level of fibrillar amyloid
(93%), insoluble beta-amyloid (Abeta; 68%), and soluble Abeta
(45%) fragments in 14-month-old mice treated with Protollin beginning at
age 5 months. Twenty-four-month-old mice treated with nasal Protollin for
6 weeks had decreased soluble and insoluble Abeta (1-40) and (1-42) and
improved memory function. Activated microglia (CD11b(+) cells) colocalized
with Abeta fibrils in the 24-month-old animals, and microglial activation
correlated with the decrease in Abeta. No microglial activation was
observed in 14-month-old mice, suggesting that once Abeta is cleared,
there is downregulation of microglial activation. Both groups had
reduction in astrocytosis. Protollin was observed in the nasal cavity and
cervical lymph node but not in the brain. Activated
CD11b(+)SRA(+) (scavenger receptor A) cells were found in blood and
cervical lymph node and increased interleukin-10 in cervical lymph
node. No toxicity was associated with treatment. INTERPRETATION: Our
results demonstrate a novel antibody-independent immunotherapy for both
prevention and treatment of Alzheimer's disease that is mediated by
peripheral activation of microglia with no apparent toxicity. Ann Neurol
2008;63:591-601.
PMID: 18360829

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